酒精对背侧纹状体突触可塑性的影响及其机制研究
|
摘要
药物滥用是现今世界范围内危害人类健康、危及社会安定的重要医学和社会学问题,成瘾物质的奖赏和增强作用使患者不顾风险地吸食,尤其是欣快和解忧的快感在中枢留下清晰记忆导致患者复吸。复吸通常发生在当成瘾者重新遇到和他以前服药时相关的人、事、地点等暗示信号的时候,这提示成瘾过程中可能出现了由药物诱导的行为和神经元突触可塑性的病态稳定形式,这种突触可塑性可视为学习记忆的一种特殊形式:在药物作用下,神经元和神经网络发生可塑性变化从而产生特定的习得性行为,并形成记忆痕迹,储存在脑的奖赏和记忆系统里。因此,成瘾也被认为是一种病态的学习和记忆过程,以失控的主动寻药和强迫性用药为特征的脑和行为方式的紊乱。酒精是迄今使用时间最长、范围最广泛的成瘾药物,但其中枢作用机制仍留有许多未知有待阐释。
中枢神经系统对成瘾物质大多产生两种反应:神经适应性反应和突触可塑性变化。然而,过去几十年的研究大多集中在中枢对成瘾物质神经适应性反应方面,而较少关注突触可塑性变化以及联合型学习机制。长时程增强(long term potatiation,LTP)被公认为突触传递易化重要的电生理指标,作为持久形式的突触可塑性反映突触水平上信息储存过程,是记忆巩固过程中神经元生理活动的客观指标之一。虽然成瘾时神经元突触长时改变与学习记忆系统的LTP很相似,但前者诱导的LTP是病理性的。
围绕在大脑皮层、基底神经节、丘脑间,并与多种神经结构形成复杂神经网络的纹状体近年来被认为是药物滥用的主要靶区,有研究认为,从中脑VTA向背侧纹状体投射的多巴胺系统涉及到学习记忆形成和行为习惯的执行。因此,对背侧纹状体的观念发生了重大改变,认为它也是成瘾习惯形成的中心脑区:以其中储藏的多巴胺作为信号固化模式可导致患者向强迫性、习惯性行为模式转化,完成从偶而用药向强迫性服药行为转化。
近年被分析出来的一个信号级联MAPK级联(MAPKkk、MAPKk、MAPK)广泛分布于细胞浆内,具有丝氨酸和苏氨酸双重磷酸化能力,由不同的细胞外刺激介导细胞表面至细胞核激活,是细胞内重要的信号传递者,现有较多的研究只是注意到它与细胞生长、分化、增殖和肿瘤形成有关,在海马上的研究发现MAPK能参与调控神经元多种活动包括学习记忆。但MAPK信号级联是否在药物成瘾的长时程记忆中起重要作用则有待进一步研究。
因此,本研究的目的在于阐释酒精如何影响背侧纹状体的突触可塑性:首先观察背侧纹状体突触可塑性的表现及其与膜受体的关系;其次研究酒精是否对其产生影响以及与酒精剂量的关系;最后阐明酒精影响背侧纹状体突触可塑性的细胞内机制是否涉及MAPK信号通路。
第一部分背侧纹状体长时程增强(LTP)的诱导及其与NMDA受体的关系
目的:研究强直刺激(HFS)在背侧纹状体所诱导的突触可塑性表现及其与膜NMDA受体的相关性。
方法:SD大鼠制备脑片47张(大鼠15只),随机分为4组:对照组(正常ACSF灌流)脑片25张;无Mg2+组(去Mg2+ACSF灌流)脑片8张;MK801组(MK801 20μM处理脑片)脑片9张;AP5组(AP5 50μM处理脑片)脑片5张。脑片均施加HFS,参数为:4串,串长1s,频率100Hz,每串间隔20s,刺激波宽0.1ms,刺激强度为最大刺激强度的1.2-1.4倍,约为180-250μA,观察各组可塑性表现。
结果:各组脑片HFS之后第60 min的记录到的PS幅值增加,在对照组为刺激前的145±14 %,25张脑片中15张表现为LTP,10张无改变;在无Mg2+组为刺激前的126±5 %,8张脑片中6张表现为LTP,2张无改变;在MK801组为刺激前的104±5%,均未表现出LTP;在AP5组幅值为刺激前的105±4%,未表现出LTP。
结论:HFS可在背侧纹状体稳定地诱导出LTP,这种LTP经由膜受体NMDA受体介导。
第二部分不同浓度酒精对背侧纹状体PS和LTP的影响
目的:观察酒精对背侧纹状体PS以及LTP的影响及其与酒精浓度的关系。
方法:SD大鼠制备脑片77张(大鼠36只),随机分为5组:对照组(正常ACSF灌流脑片)脑片25张;22 mM组(以22 mM酒精灌流脑片)5张予测试刺激,6张予强直刺激;44 mM组(以44 mM酒精灌流脑片)5张予测试刺激,7张予强直刺激;66 mM组(以66 mM酒精灌流脑片)7张予测试刺激,8张予强直刺激;88 mM组(以88 mM酒精灌流脑片)9张予测试刺激,5张予强直刺激。HFS的参数同实验一,观察各组PS以及LTP的变化。
结果:脑片用不同浓度酒精灌流和洗脱处理,施以测试刺激,第60 min的PS幅值在22、44、66、88 mM组分别为灌流前的100.2±1.3%、97.6±3.2%、95.4±3.0%、91.2±6.3% ;脑片以不同浓度酒精灌流处理15 min,施以HFS之后第60 min的PS幅值在22、44、66、88 mM组分别增加为刺激前的124±10%、113±13%、98±5%、94±7%。
结论:酒精在背侧纹状体对HFS所致LTP的抑制呈剂量相关性,酒精本身对PS的影响与这种抑制无关,但可能影响了LTP的大小。
第三部分酒精抑制背侧纹状体LTP与MAPK信号通路关系的研究
目的:研究酒精对背侧纹状体LTP的抑制与细胞内MAPK(ERK和JNK)信号通路的关系。
方法:SD大鼠制备脑片162张(大鼠72只),随机分9组:对照组(正常ACSF灌流脑片)脑片46张;DMSO溶剂对照组脑片14张;U0126灌流组脑片18张;22 mM酒精灌流组脑片8张;44 mM酒精灌流组脑片8张;66 mM酒精灌流组脑片40张;88 mM酒精灌流组脑片8张;MK801灌流组脑片12张;SP600125灌流组脑片8张,采用电生理技术记录并在电生理实验后收集脑片以western blotting方法检测蛋白含量,HFS的参数同实验一。
结果:给予强直刺激后的第10分钟,与刺激前相比,对照组脑片ERK磷酸化明显增强,并在第60分钟恢复为正常水平;而用ERK抑制剂U0126处理脑片,在抑制ERK活性同时也阻止了强直刺激后LTP的诱导。如果不施加强直刺激,不同浓度酒精灌流脑片并不会引起ERK基础磷酸化水平的改变;而在强直刺激后10 min,22、44 mM的酒精处理组ERK磷酸化与对照组相比无明显区别;66、88 mM的酒精灌流可以抑制强直刺激所致之ERK磷酸化;并且在强直刺激后的第60 min,66 mM酒精处理组ERK磷酸化恢复为正常水平。以MK801处理脑片可以抑制强直刺激后第10min的ERK磷酸化,这种效果在第60 min消失,ERK磷酸化恢复为正常水平。另一方面,在背内侧纹状体,以JNK抑制剂SP600125灌流脑片30 min(30 min pre-HFS),并不影响LTP的诱导。在不同条件下检测JNK活性,发现对照组pJNK(46kD)和pJNK(54kD)的水平在强直刺激前、强直刺激后的10 min、20 min、60 min都无明显改变;在66 mM酒精处理的脑片中,强直刺激前后其JNK活性与对照组相比也无明显区别。
结论:MAPK信号通路家族中ERK激酶参与了经NMDA受体介导之酒精对纹状体HFS-LTP诱导的剂量相关性抑制效应,而JNK激酶则与此无明显相关性。
综上所述,本文工作的主要创新之处在于:
1、本研究发现,与习惯形成密切相关的背侧纹状体,是酒精作用的中枢靶区之一;HFS可在纹状体稳定地诱导LTP,这一LTP是经膜NMDA受体介导的。
2、观察了不同浓度的酒精(22--88 mM)呈剂量依赖性抑制LTP的诱导,其中66 mM抑制效果最强和稳定。
3、用western blot方法观察了LTP诱导和维持的不同时期表达的变化,以及酒精对其的影响,发现酒精是通过降低HFS所致MAPK/ERK活性增强进而抑制LTP的诱导,而与MAPK/JNK活性无关。
Ethanol is a widely used and abused drug that affects learning and behavior and can induce an acute amnestic state. Compared to the effects of other addictive substances such as cocaine and nicotine, the effects of ethanol are more diffuse, including diverse documented effects on various ligand-gated and voltage-gated channels. Consequently, the mechanisms underlying ethanol’s actions on the central nervous system are difficult to pin down, and a greater understanding of these mechanisms might provide a foundation for new treatments for alcoholism.
Clinical and laboratory observations have proposed that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. Long-term potentiation (LTP) enhances learning and long-term memory by strengthening the synapse, the point through which nervous impulses pass from one neuron to another. Long-term depression (LTD) is essentially the opposite, weakening the neuronal synapse. Therefore, LTP and LTD have become an important focus of addiction research. Reward-guided behaviors are often attributed to the cortico-basal ganglia networks coursing through the neostriatum. The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. However, the involvement of the dorsomedial striatum (DMS) in acute drug abuse has not received much attention, and the mechanisms underlying the effects of acute ethanol on corticostriatal plasticity still remain unclear.
Extracellular signal regulated protein kinases (ERKs), which are mitogen activated protein kinases (MAPKs) that are 44 and 42 kD, are involved in diverse forms of neuronal plasticity. Recently, evidence has pointed to ERKs as having a role in the LTPs that occur in the CA1 region of the hippocampus. The MAPK?ERK signal transduction pathway follows the binding of growth factors to receptors on the cell’s surface to its intracellular responses. Several studies suggested the ERK signal transduction pathway as a potential cellular target of ethanol. Alterations in ERKs could play an important role in the chronic alcoholinduced changes in synaptic plasticity. These findings raise the possibility that ERK activation may contribute to the striatal LTP induction and to the effects of acute ethanol on corticostriatal plasticity. To test this possibility, we studied the high-frequency afferent stimulation (HFS) - induced ERK activation in acute ethanol-treated slices from the rat DMS. We also examined the effects of the N-methyld- aspartic acid receptor (NMDAR) antagonist MK801 on ERK activation in this brain region.c-Jun N-terminal kinase (JNKs), another kind of MAPKs, are involved in diverse forms of neuronal plasticity, too. We tested the alteration of JNK activation in this work, too.
Part I Long-term potentiation induced by HFS in striatum of rat
AIM:To investigate striatal synaptic plasticity involved in instrumental learning.
METHODS:The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS).
RESULTS:HFS evoked obvious LTPs both in the slices incubated with ACSF and ACSF without Mg2+. MK801 and APV, N-methyl-d-aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTPs.
CONCLUSION:The LTP of the PS in the DMS is, at least partly, mediated by NMDARs.
Part II Effects of different concentrations of ethanol on the striatal
LTP
AIM: The objective of this investigation was to study the effects of acute perfusion of ethanol on PS and long term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum.
METHODS: The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS).
RESULTS: Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP in this brain region. 22, 44, 66 and 88 mM of ethanol induced a change in PS amplitude by 0.2±1.3% (p = 0.37, n = 5), -2.4±3.2% (p = 0.07, n = 5), -4.6±3.0% (p < 0.05, n = 7) and -8.4±6.3% (p < 0.05, n = 9), respectively. All these changes returned to the baseline levels after washout of ethanol. The PS amplitude before HFS (baseline PS) was compared to that recorded 60 min after HFS. The PS amplitudes at 60 min after HFS increased to 145±14% of the baseline value (n = 14) in the slices under control conditions. After the perfusion of 22, 44, 66 and 88 mM ethanol, the PS amplitudes at 60 min post-HFS were 124±10% (n = 6), 113±13% (n = 7), 98±5% ( n = 8), 94±7% (n = 4) of the pre-HFS baseline values, respectively.
CONCLUSION: Ethanol attenuated the HFS-induced LTP in a dosedependent manner in this brain region.
Part III Effects of ethanol on the striatal LTP involved in the MAPKs
activation
AIM: To study the effects of acute perfusion of ethanol on long term potentiation (LTP) as well as to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of both ERKs and JNKs signaling pathways to corticostriatal LTP induction.
METHODS: The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). Both the ERKs and JNKs levels of the DMS were assessed with the Western blot technique.
RESULTS: U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N-methyl-d-aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region. On the other hand, SP600125, the inhibitor of JNK, had no effect on the striatal LTP. Furthermore, ethanol (66 mM) did not show any effect on JNK activation before or after HFS in the DMS.
CONCLUSION: The LTP of the PS in the DMS is, at least partly, mediated by the ERK (but not JNK) pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region.
In summary, the present study reports for the first time that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs.
中枢神经系统对成瘾物质大多产生两种反应:神经适应性反应和突触可塑性变化。然而,过去几十年的研究大多集中在中枢对成瘾物质神经适应性反应方面,而较少关注突触可塑性变化以及联合型学习机制。长时程增强(long term potatiation,LTP)被公认为突触传递易化重要的电生理指标,作为持久形式的突触可塑性反映突触水平上信息储存过程,是记忆巩固过程中神经元生理活动的客观指标之一。虽然成瘾时神经元突触长时改变与学习记忆系统的LTP很相似,但前者诱导的LTP是病理性的。
围绕在大脑皮层、基底神经节、丘脑间,并与多种神经结构形成复杂神经网络的纹状体近年来被认为是药物滥用的主要靶区,有研究认为,从中脑VTA向背侧纹状体投射的多巴胺系统涉及到学习记忆形成和行为习惯的执行。因此,对背侧纹状体的观念发生了重大改变,认为它也是成瘾习惯形成的中心脑区:以其中储藏的多巴胺作为信号固化模式可导致患者向强迫性、习惯性行为模式转化,完成从偶而用药向强迫性服药行为转化。
近年被分析出来的一个信号级联MAPK级联(MAPKkk、MAPKk、MAPK)广泛分布于细胞浆内,具有丝氨酸和苏氨酸双重磷酸化能力,由不同的细胞外刺激介导细胞表面至细胞核激活,是细胞内重要的信号传递者,现有较多的研究只是注意到它与细胞生长、分化、增殖和肿瘤形成有关,在海马上的研究发现MAPK能参与调控神经元多种活动包括学习记忆。但MAPK信号级联是否在药物成瘾的长时程记忆中起重要作用则有待进一步研究。
因此,本研究的目的在于阐释酒精如何影响背侧纹状体的突触可塑性:首先观察背侧纹状体突触可塑性的表现及其与膜受体的关系;其次研究酒精是否对其产生影响以及与酒精剂量的关系;最后阐明酒精影响背侧纹状体突触可塑性的细胞内机制是否涉及MAPK信号通路。
第一部分背侧纹状体长时程增强(LTP)的诱导及其与NMDA受体的关系
目的:研究强直刺激(HFS)在背侧纹状体所诱导的突触可塑性表现及其与膜NMDA受体的相关性。
方法:SD大鼠制备脑片47张(大鼠15只),随机分为4组:对照组(正常ACSF灌流)脑片25张;无Mg2+组(去Mg2+ACSF灌流)脑片8张;MK801组(MK801 20μM处理脑片)脑片9张;AP5组(AP5 50μM处理脑片)脑片5张。脑片均施加HFS,参数为:4串,串长1s,频率100Hz,每串间隔20s,刺激波宽0.1ms,刺激强度为最大刺激强度的1.2-1.4倍,约为180-250μA,观察各组可塑性表现。
结果:各组脑片HFS之后第60 min的记录到的PS幅值增加,在对照组为刺激前的145±14 %,25张脑片中15张表现为LTP,10张无改变;在无Mg2+组为刺激前的126±5 %,8张脑片中6张表现为LTP,2张无改变;在MK801组为刺激前的104±5%,均未表现出LTP;在AP5组幅值为刺激前的105±4%,未表现出LTP。
结论:HFS可在背侧纹状体稳定地诱导出LTP,这种LTP经由膜受体NMDA受体介导。
第二部分不同浓度酒精对背侧纹状体PS和LTP的影响
目的:观察酒精对背侧纹状体PS以及LTP的影响及其与酒精浓度的关系。
方法:SD大鼠制备脑片77张(大鼠36只),随机分为5组:对照组(正常ACSF灌流脑片)脑片25张;22 mM组(以22 mM酒精灌流脑片)5张予测试刺激,6张予强直刺激;44 mM组(以44 mM酒精灌流脑片)5张予测试刺激,7张予强直刺激;66 mM组(以66 mM酒精灌流脑片)7张予测试刺激,8张予强直刺激;88 mM组(以88 mM酒精灌流脑片)9张予测试刺激,5张予强直刺激。HFS的参数同实验一,观察各组PS以及LTP的变化。
结果:脑片用不同浓度酒精灌流和洗脱处理,施以测试刺激,第60 min的PS幅值在22、44、66、88 mM组分别为灌流前的100.2±1.3%、97.6±3.2%、95.4±3.0%、91.2±6.3% ;脑片以不同浓度酒精灌流处理15 min,施以HFS之后第60 min的PS幅值在22、44、66、88 mM组分别增加为刺激前的124±10%、113±13%、98±5%、94±7%。
结论:酒精在背侧纹状体对HFS所致LTP的抑制呈剂量相关性,酒精本身对PS的影响与这种抑制无关,但可能影响了LTP的大小。
第三部分酒精抑制背侧纹状体LTP与MAPK信号通路关系的研究
目的:研究酒精对背侧纹状体LTP的抑制与细胞内MAPK(ERK和JNK)信号通路的关系。
方法:SD大鼠制备脑片162张(大鼠72只),随机分9组:对照组(正常ACSF灌流脑片)脑片46张;DMSO溶剂对照组脑片14张;U0126灌流组脑片18张;22 mM酒精灌流组脑片8张;44 mM酒精灌流组脑片8张;66 mM酒精灌流组脑片40张;88 mM酒精灌流组脑片8张;MK801灌流组脑片12张;SP600125灌流组脑片8张,采用电生理技术记录并在电生理实验后收集脑片以western blotting方法检测蛋白含量,HFS的参数同实验一。
结果:给予强直刺激后的第10分钟,与刺激前相比,对照组脑片ERK磷酸化明显增强,并在第60分钟恢复为正常水平;而用ERK抑制剂U0126处理脑片,在抑制ERK活性同时也阻止了强直刺激后LTP的诱导。如果不施加强直刺激,不同浓度酒精灌流脑片并不会引起ERK基础磷酸化水平的改变;而在强直刺激后10 min,22、44 mM的酒精处理组ERK磷酸化与对照组相比无明显区别;66、88 mM的酒精灌流可以抑制强直刺激所致之ERK磷酸化;并且在强直刺激后的第60 min,66 mM酒精处理组ERK磷酸化恢复为正常水平。以MK801处理脑片可以抑制强直刺激后第10min的ERK磷酸化,这种效果在第60 min消失,ERK磷酸化恢复为正常水平。另一方面,在背内侧纹状体,以JNK抑制剂SP600125灌流脑片30 min(30 min pre-HFS),并不影响LTP的诱导。在不同条件下检测JNK活性,发现对照组pJNK(46kD)和pJNK(54kD)的水平在强直刺激前、强直刺激后的10 min、20 min、60 min都无明显改变;在66 mM酒精处理的脑片中,强直刺激前后其JNK活性与对照组相比也无明显区别。
结论:MAPK信号通路家族中ERK激酶参与了经NMDA受体介导之酒精对纹状体HFS-LTP诱导的剂量相关性抑制效应,而JNK激酶则与此无明显相关性。
综上所述,本文工作的主要创新之处在于:
1、本研究发现,与习惯形成密切相关的背侧纹状体,是酒精作用的中枢靶区之一;HFS可在纹状体稳定地诱导LTP,这一LTP是经膜NMDA受体介导的。
2、观察了不同浓度的酒精(22--88 mM)呈剂量依赖性抑制LTP的诱导,其中66 mM抑制效果最强和稳定。
3、用western blot方法观察了LTP诱导和维持的不同时期表达的变化,以及酒精对其的影响,发现酒精是通过降低HFS所致MAPK/ERK活性增强进而抑制LTP的诱导,而与MAPK/JNK活性无关。
Ethanol is a widely used and abused drug that affects learning and behavior and can induce an acute amnestic state. Compared to the effects of other addictive substances such as cocaine and nicotine, the effects of ethanol are more diffuse, including diverse documented effects on various ligand-gated and voltage-gated channels. Consequently, the mechanisms underlying ethanol’s actions on the central nervous system are difficult to pin down, and a greater understanding of these mechanisms might provide a foundation for new treatments for alcoholism.
Clinical and laboratory observations have proposed that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. Long-term potentiation (LTP) enhances learning and long-term memory by strengthening the synapse, the point through which nervous impulses pass from one neuron to another. Long-term depression (LTD) is essentially the opposite, weakening the neuronal synapse. Therefore, LTP and LTD have become an important focus of addiction research. Reward-guided behaviors are often attributed to the cortico-basal ganglia networks coursing through the neostriatum. The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. However, the involvement of the dorsomedial striatum (DMS) in acute drug abuse has not received much attention, and the mechanisms underlying the effects of acute ethanol on corticostriatal plasticity still remain unclear.
Extracellular signal regulated protein kinases (ERKs), which are mitogen activated protein kinases (MAPKs) that are 44 and 42 kD, are involved in diverse forms of neuronal plasticity. Recently, evidence has pointed to ERKs as having a role in the LTPs that occur in the CA1 region of the hippocampus. The MAPK?ERK signal transduction pathway follows the binding of growth factors to receptors on the cell’s surface to its intracellular responses. Several studies suggested the ERK signal transduction pathway as a potential cellular target of ethanol. Alterations in ERKs could play an important role in the chronic alcoholinduced changes in synaptic plasticity. These findings raise the possibility that ERK activation may contribute to the striatal LTP induction and to the effects of acute ethanol on corticostriatal plasticity. To test this possibility, we studied the high-frequency afferent stimulation (HFS) - induced ERK activation in acute ethanol-treated slices from the rat DMS. We also examined the effects of the N-methyld- aspartic acid receptor (NMDAR) antagonist MK801 on ERK activation in this brain region.c-Jun N-terminal kinase (JNKs), another kind of MAPKs, are involved in diverse forms of neuronal plasticity, too. We tested the alteration of JNK activation in this work, too.
Part I Long-term potentiation induced by HFS in striatum of rat
AIM:To investigate striatal synaptic plasticity involved in instrumental learning.
METHODS:The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS).
RESULTS:HFS evoked obvious LTPs both in the slices incubated with ACSF and ACSF without Mg2+. MK801 and APV, N-methyl-d-aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTPs.
CONCLUSION:The LTP of the PS in the DMS is, at least partly, mediated by NMDARs.
Part II Effects of different concentrations of ethanol on the striatal
LTP
AIM: The objective of this investigation was to study the effects of acute perfusion of ethanol on PS and long term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum.
METHODS: The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS).
RESULTS: Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP in this brain region. 22, 44, 66 and 88 mM of ethanol induced a change in PS amplitude by 0.2±1.3% (p = 0.37, n = 5), -2.4±3.2% (p = 0.07, n = 5), -4.6±3.0% (p < 0.05, n = 7) and -8.4±6.3% (p < 0.05, n = 9), respectively. All these changes returned to the baseline levels after washout of ethanol. The PS amplitude before HFS (baseline PS) was compared to that recorded 60 min after HFS. The PS amplitudes at 60 min after HFS increased to 145±14% of the baseline value (n = 14) in the slices under control conditions. After the perfusion of 22, 44, 66 and 88 mM ethanol, the PS amplitudes at 60 min post-HFS were 124±10% (n = 6), 113±13% (n = 7), 98±5% ( n = 8), 94±7% (n = 4) of the pre-HFS baseline values, respectively.
CONCLUSION: Ethanol attenuated the HFS-induced LTP in a dosedependent manner in this brain region.
Part III Effects of ethanol on the striatal LTP involved in the MAPKs
activation
AIM: To study the effects of acute perfusion of ethanol on long term potentiation (LTP) as well as to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of both ERKs and JNKs signaling pathways to corticostriatal LTP induction.
METHODS: The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). Both the ERKs and JNKs levels of the DMS were assessed with the Western blot technique.
RESULTS: U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N-methyl-d-aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region. On the other hand, SP600125, the inhibitor of JNK, had no effect on the striatal LTP. Furthermore, ethanol (66 mM) did not show any effect on JNK activation before or after HFS in the DMS.
CONCLUSION: The LTP of the PS in the DMS is, at least partly, mediated by the ERK (but not JNK) pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region.
In summary, the present study reports for the first time that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs.
引文
507-13
[12]. Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J. Neural systems and cue-induced cocaine craving. Neuropsychopharmacology, 2002 (26): 376-86
[13]. Kelley AE, Berridge KC. The neuroscience of natural rewards: relevance to addictive drugs. J. Neurosci. 2002(22): 3306-11
[14]. Berke JD, Sgambato V, Zhu P-P, Lavoie B, Vincent M. Dopamine and glutamate induce distinct striatal splice forms of ania-6, an RNA polymerase II-associated cyclin. Neuron . 2001 (32): 1-20
[15]. Everitt BJ, Dickinson A, Robbins TW. The neuropsychological basis of addictive behaviour. Brain Res. Brain Res. Rev. 2001, 36 (2-3):129-138
[16]. Paulus MP, Tapert SF, Schuckit MA. Neural activation patterns of methamphetaminedependent subjects during decision making predict relapse. Arch. Gen. Psychiatry, 2005, 62(7): 761-768
[17]. Robinson S, Sandstrom SM, Denenberg VH, Palmiter RD. Distinguishing whether dopamine regulates liking, wanting, and/or learning about rewards. Behav. Neurosci. 2005(199): 336-341
[18]. Bayer HM, Glimcher PW. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron, 2005, 47(1): 129-141
[19]. Semenova S, Markou A. Cocaine-seeking behavior after extended cocaine-free periods in rats: role of conditioned stimuli. Psychopharmacology, 2003(168): 192-200
[20]. Borgland SL, Malenka RC, Bonci A. Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: electrophysiological and behavioral correlates in individual rats. J. Neurosci. 2004(24): 7482-490
[21]. Everitt BJ, Wolf ME. Psychomotor stimulant addiction: a neural systems perspective. J. Neurosci. 2002, 22(9): 3312-20
[22]. Hnasko TS, Sotak BN, Palmiter RD. Morphine reward in dopamine-deficientmice. Nature 2005(438): 854-57
[23]. Kringelbach ML. The human orbitofrontal cortex: linking reward to hedonic experience. Nat. Rev. Neurosci. 2005, 6(9): 691-702
[24]. Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry , 2002(159): 1642-52
[25]. Gottfried JA, O’Doherty J, Dolan RJ. Encoding predictive reward value in human amygdale and orbitofrontal cortex. Science, 2003(301): 1104-7
[26]. Faleiro LJ, Jones S, Kauer JA. Rapid synaptic plasticity of glutamatergic synapses on dopamine neurons in the ventral tegmental area in response to acute amphetamine injection. Neuropsychopharmacology, 2004(29): 2115-25
[27]. Harris GC, Aston-Jones G. Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment. Neuropsychopharmacology, 2003(28): 73-76
[28]. Kauer JA. Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu. Rev. Physiol. 2004(66): 447-75
[29]. Kalivas PW, Volkow N, Seamans J. Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron. 2005(45): 647-50
[30]. Everitt BJ, Cardinal RN, Parkinson JA, Robbins TW. Appetitive behavior: impact of amygdala-dependent mechanisms of emotional learning. Ann. N. Y. Acad. Sci. 2003(985): 233-50
[31]. Dumont EC, Mark GP, Mader S, Williams JT. Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis. Nat. Neurosci. 2005(8): 413-14
[32]. Deroche-Gamonet V, Belin D, Piazza PV. Evidence for addiction-like behavior in the rat. Science. 2004(305): 1014-17
[33]. Carlezon WA Jr, Nestler EJ. Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse? Trends Neurosci. 2002(25): 610-15
[34]. Cannon CM, Palmiter RD. Reward without dopamine. J. Neurosci. 2003(23): 10827-31
[35]. Di Chiara G. A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use. J. Psychopharmacol. 1998(12): 54-67
[36]. Kumar A, Choi K-H, Renthal W, Tsankova NM, Theobald DEH. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron. 2005(48): 303-14
[37]. Matsumoto K, Suzuki W, Tanaka K. Neuronal correlates of goal-based motor selection in the prefrontal cortex. Science. 2003(301): 229-32
[38]. Yin, H.H. & Knowlton, B.J. Contributions of striatal subregions to place and response learning. Learn. Mem., 2004(11) : 459-463.
[39]. Yin, H.H. & Knowlton, B.J. The role of the basal ganglia in habit formation. Nature Rev. Neurosci. 2006(7): 464-476.
[40]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning. Eur. J. Neurosci., 2004(19): 181-189.
[41]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning. Eur. J. Neurosci., 2005a(22): 505-512.
[42]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning. Behav. Brain Res., 2006(166): 189-196.
[43]. Yin, H.H., Ostlund, S.B., Knowlton, B.J. & Balleine, B.W. The role of the dorsomedial striatum in instrumental conditioning. Eur. J. Neurosci., 2005b(22): 513-523
[44]. Chklovskii DB, Mel BW, Svoboda K. Cortical rewiring and information storage.Nature, 2004(431): 782-88
[45]. Choi KH, Rahman Z, Edwards S, Hall S, Neve RL, Self DW. Opposite effects of GluR1 and PKA-resistant GluR1 overexpression in the ventral tegmental area on cocaine reinforcement. Ann. N. Y. Acad. Sci. 2003(1003): 372-74
[46]. Barnes TD, Kubota Y, Hu D, Jon DZ, Graybiel AM. Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories. Nature 2005(437): 1158-61
[47]. Atallah, H.E., Lopez-Paniagua, D., Rudy, J.W. & O’Reilly, R.C. Separate neural substrates for skill learning and performance in the ventral and dorsal striatum. Nature Neurosci., 2007(10): 126-131
[48]. Bailey, K.R. & Mair, R.G. The role of striatum in initiation and execution of learned action sequences in rats. J. Neurosci., 2006 (26): 1016-1025
[49]. Brebner K, Wong TP, Liu L, Liu Y, Campsall P. Nucleus accumbens long-term depression and the expression of behavioral sensitization. Science 2005 (310): 1340-43
[50]. Bliss, T.V.P. & Collingridge, G.L. A synaptic model of memory: longterm potentiation in the hippocampus. Nature, 1993(361): 31-39.
[51]. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron, 2004(44): 5-21
[52]. Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 2000(23): 649-711
[53]. Welsby PJ, Rowan MJ, Anwyl R. Intracellular mechanisms underlying the nicotinic enhancement of LTP in the rat dentate gyrus. Eur J Neurosci. 2009, 29(1):65-75.
[54]. Kalivas PW. Glutamate systems in cocaine addiction. Curr. Opin. Pharmacol. 2004(4): 23-29
[55]. Szumlinski KK, Dehoff MH, Kang SH. Homer proteins regulate sensitivity to cocaine. Neuron. 2004(43): 401-13
[56]. Hope B, Kosofsky B, Hyman SE, Nestler EJ. Regulation of IEG expression and AP-1 binding by chronic cocaine in the rat nucleus accumbens. Proc. Natl. Acad. Sci. USA, 1992(89): 5764-68
[57]. Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat. Rev. Genet. 2005(6): 521-32
[58]. Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW. Striatal cell type-specific overexpression of FosB enhances incentive for cocaine. J. Neurosci. 2003, 23(6): 2488-93
[59]. Daunais JB, McGinty JF. Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs. Synapse, 1994(18): 35-46
[60]. Chao J, Nestler EJ. Molecular neurobiology of drug addiction. Annu. Rev. Med. 2004(55): 113-32
[61]. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS. Defining the CREB regulon: a genome-wide analysis of transcription factor regulator regions. Cell, 2004(119): 1041-54
[62]. McClung CA, Nestler EJ. Regulation of gene expression and cocaine reward by CREB and FosB. Nat. Neurosci. 2003(6): 1208-15
[63]. Kelz MB, Chen JS, Carlezon WA Jr, Whisler K, Gilden L. Expression of the transcription factor FosB in the brain controls sensitivity to cocaine. Nature 1999(401): 272-76
[64]. Olson VG, Zabetian CP, Bolanos CA, Edwards S, Barrot M, et al. Regulation of drug reward byCREB:evidence for two functionally distinct subregions of the ventral tegmental area. J. Neurosci. 2005(25): 5553-62
[65]. Carlezon WA Jr, Duman RS, Nestler EJ. The many faces of CREB. Trends Neurosci. 2005(28): 436-45
[66]. Brunzell DH, Russell DS, Picciotto MR. In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice. J. Neurochem.2003(84): 1431-41
[67]. Zhang X, OdomDT, Koo SH, Conkright MD, Canettieri G. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc. Natl. Acad. Sci. 2005, 102(12): 4459-64
[68]. Walters CL, Kuo YC, Blendy JA. Differential distribution of CREB in the mesolimbic dopamine reward pathway. J. Neurochem. 2003(87): 1237-44
[69]. Roberson, E.D., English, J.D., Adams, J.P., Selcher, J.C., Kondratick, C. & Sweatt, J.D. The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus. J. Neurosci., 1999(19): 4337-4348.
[70]. Huang YH, Lin Y, Brown TE, Han MH, Saal DB, Neve RL, Zukin RS, Sorg BA, Nestler EJ, Malenka RC, Dong Y. CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors. J Biol Chem. 2008, 283 (5): 2751-60
[71]. Konradi C, Leveque JC, Hyman SE. Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium. J. Neurosci. 1996(16): 4231-39
[72]. Shaw-Lutchman TZ, Impey S, Storm D, Nestler EJ. Regulation of CRE-mediated transcription in mouse brain by amphetamine. Synapse, 2003(48): 10-17
[73]. Walters CL, Cleck JN, Kuo YC, Blendy JA.μ-opioid receptor and CREB activation are required for nicotine reward. Neuron, 2005(16): 933-43
[74]. Zachariou V, Bolanos CA, Selley DE, Theobald D, Cassidy MP, et al. FosB: an essential role for FosB in the nucleus accumbens in morphine action. Nat. Neurosci. 2006(9): 205-11
[75]. Boulton, T.G., Nye, S.H., Robbins, D.J., Ip, N.Y., Radziejewska, E., Morgenbesser, S.D., DePinho, R.A., Panayotatos, N., Cobb, M.H. &Yancopoulos, G.D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell, 1991(65): 663-675.
[76]. Blum, S., Moore, A.N., Adams, F. & Dash, P.K. A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory. J. Neurosci., 1999(19): 3535-3544.
[77]. Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev., 2000(80): 953-978.
[78]. Barrot M, Olivier JDA, Perrotti LI, Impey S, Storm DR, et al. CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Proc. Natl. Acad. Sci. 2002(99): 11435-40
[79]. Ito R, Robbins TW, Everitt BJ. Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat. Neurosci. 2004, 7(4): 389-97
[80]. Packard MG, Knowlton BJ. Learning and memory functions of the basal ganglia. Annu. Rev. Neurosci. 2002(25): 563-93
[81]. White, N.M. Mnemonic functions of the basal ganglia. Curr. Opin. Neurobiol., 1997(7): 164-169.
[82]. Partridge, J.G., Tang, K.C. & Lovinger, D.M. Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum. J. Neurophysiol., 2000(84): 1422-1429.
[83]. Nicoll, R.A. Expression mechanisms underlying long-term potentiation: a postsynaptic view. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2003(358): 721-726.
[84]. Kreitzer A, Malenka RC. Dopamine modulation of state-dependent endocannabinoid release and LTD in the striatum. J. Neurosci. 2005(25): 10537-45
[85]. Kombian SB, Malenka RC. Simultaneous LTP of non-NMDA- and LTD ofNMDAreceptor- mediated responses in the nucleus accumbens. Nature. 1994(368): 242-46
[86]. McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ. FosB: a molecular switch for long-term adaptation. Mol. Brain Res. 2004(132): 146-54
[87]. Cunningham, C.L., Howard, M.A., Gill, S.J., Rubinstein, M., Low, M.J. & Grandy, D.K. Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice. Pharmacol. Biochem. Behav., 2000(67): 693-699.
[88]. Dang, M.T., Yokoi, F., Yin, H.H., Lovinger, D.M., Wang, Y. & Li, Y. Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum. Proc. Natl Acad. Sci. 2006(103): 15254-15259.
[89]. Reynolds, J.N., Hyland, B.I. & Wickens, J.R. A cellular mechanism of reward-related learning. Nature, 2001(413): 67-70.
[90]. Kobayashi, T., Ikeda, K., Kojima, H., Niki, H., Yano, R., Yoshioka, T. & Kumanishi, T. Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nature Neurosci., 1999(2): 1091-1097.
[91]. Lovinger, D.M., White, G. & Weight, F.F. Ethanol inhibits NMDAactivated ion current in hippocampal neurons. Science, 1989(243): 1721-1724.
[92]. Lovinger, D.M. Alcohols and neurotransmitter gated ion channels: past, present and future. Naunyn Schmiedebergs Arch. Pharmacol., 1997(356): 267-282.
[93]. Schultz W. Behavioral theories and the neurophysiology of reward. Annu. Rev. Psychol. 2006(57): 87-11
[94]. Self DW. Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system. Neuropharmacology, 2004(47, Suppl. 1): 242-55
[95]. Schummers J., Bentz S. Browning, M.D. Ethanol’s inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor. Alcohol Clin. Exp. Res., 1997(21): 404-408.
[96]. Morrisett, R.A. & Swartzwelder, H.S. Attenuation of hippocampal longtermpotentiation by ethanol: a patch-clamp analysis of glutamatergic and GABAergic mechanisms. J. Neurosci., 1993(13): 2264-2272.
[97]. Henry H. Yin, Brian S. Park, Louise Adermark and David M. Lovinger. Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum European Journal of Neuroscience, 2007(25): 3226-3232
[98]. Izumi, Y., Nagashima, K., Murayama, K. & Zorumski, C.F. Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms. Neuroscience, 2005a(136): 509-517.
[99]. Thomas MJ, Beurrier C, Bonci A, Malenka RC. Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-23
[100]. Wang, Z., Kai, L., Day, M., Ronesi, J., Yin, H.H., Ding, J., Tkatch, T., Lovinger, D.M. & Surmeier, D.J. Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron, 2006(50): 443-452.
[101]. Kerr, J.N. & Wickens, J.R. Dopamine D-1 ? D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro. J. Neurophysiol., 2001(85): 117-124.
[102]. Calabresi, P., Maj, R., Pisani, A., Mercuri, N.B. & Bernardi, G. Longterm synaptic depression in the striatum: physiological and pharmacological characterization. J. Neurosci., 1992(12): 4224-4233.
[103]. Piomelli, D. The molecular logic of endocannabinoid signalling. Nature Rev. Neurosci., 2003(4): 873-884.
[104]. Ronesi, J., Gerdeman, G.L. & Lovinger, D.M. Disruption of endocannabinoid release and striatal long-term depression by postsynapticblockade of endocannabinoid membrane transport. J. Neurosci., 2004(24): 1673-1679.
[105]. Gerdeman, G.L., Ronesi, J. & Lovinger, D.M. Postsynaptic endocannabinoids release is critical to long-term depression in the striatum. Nature Neurosci.,2002(5): 446-451.
[106]. Giuffrida, A., Parsons, L.H., Kerr, T.M., Rodriguez de Fonseca, F., Navarro, M. & Piomelli, D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature Neurosci., 1999(2): 358-363.
[107]. Kreitzer, A.C. & Malenka, R.C. Dopamine modulation of statedependent endocannabinoid release and long-term depression in the striatum. J. Neurosci., 2005(25): 10537-10545.
[108]. Schummers, J., Bentz, S. & Browning, M.D. Ethanol’s inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor. Alcohol Clin. Exp. Res., 1997(21): 404-408.
[109]. Adams, J.P. & Sweatt, J.D. Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol., 2002(42): 135-163.
[110]. Atkins, C.M., Selcher, J.C., Petraitis, J.J., Trzaskos, J.M. & Sweatt, J.D. The MAPK cascade is required for mammalian associative learning. Nature Neurosci., 1998(1): 602-609.
[111]. Kornhauser, J.M. & Greenberg, M.E. A kinase to remember: dual roles for MAP kinase in long-term memory. Neuron, 1997(18): 839-842.
[112]. Sweatt, J.D. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J. Neurochem., 2001(76): 1-10.
[113]. M. Roberto, T. E. Nelson, C. L. Ur, 1 M. Brunelli, P. P. Sanna1 and D. L. Gruol1.The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway European Journal of Neuroscience, 2003(17): 1646-1654
[114]. John M. Schmitt, Gary A. Wayman, Naohito Nozaki, and Thomas R. Soderling Calcium Activation of ERK Mediated by Calmodulin Kinase I The Journal Of Biological Chemistry, 2004. 279(23): 24064-24072
[115]. English, J.D. Sweatt, J.D. Activation of p42 mitogen-activated protein kinasein hippocampal long term potentiation. J. Biol. Chem., 1996(271): 24329-24332.
[116]. English, J.D. Sweatt, J.D. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J. Biol. Chem., 1997(272): 19103-19106.
[117]. Rosenblum, K., Futter, M., Voss, K., Erent, M., Skehel, P.A., French, P., Obosi, L., Jones, M.W. & Bliss, T.V. The role of extracellular regulated kinases I/II in late-phase long-term potentiation. J. Neurosci., 2002(22): 5432-5441.
[118]. Winder, D.G., Martin, K.C., Muzzio, I.A., Rohrer, D., Chruscinski, A., Kobilka, B. & Kandel, E.R. ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors. Neuron, 1999(24): 715-726.
[119]. Wu S.P., Lu, K.T., Chang W.C. & Gean P.W. Involvement of mitogenactivated protein kinase in hippocampal long-term potentiation. J. Biomed. Sci., 1999(6): 409-417.
[120]. Cui Y, Costa RM, Murphy GG, et al . Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell. 2008,135(3): 549-60.
[121]. Toyoda H, Zhao MG, Xu H, Wu LJ, Ren M, Zhuo M. Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex. Mol Pain. 2007(3): 36.
[122]. Roberto, M., Nelson, T.E., Ur, C.L. & Gruol, D.L. Long-term potentiation in the rat hippocampus is reversibly depressed by chronic intermittent ethanol exposure. J. Neurophysiol., 2002(87): 2385-2397.
[123]. Rosen, L.B., Ginty, D.D., Weber, M.J. Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. Neuron, 1994(12): 1207-1221.
[124]. Rosenblum, K., Futter, M., Jones, M., Hulme, E.C.& Bliss, T.V. ERKI/II regulation by the muscarinic acetylcholine receptors in neurons. J. Neurosci.,2000(20): 977-985.
[125]. Soderling, T.R., Chang, B. & Brickey, D. Cellular signaling through multifunctional Ca2t/calmodulin-dependent protein kinase II. J. Biol. Chem., 2001(276): 3719-3722.
[126]. Kanterewicz, B.I., Urban, N.N., McMahon, D.B., Norman, E.D., Giffen, L.J., Favata, M.F., Scherle, P.A., Trzskos, J.M., Barrionuevo, G. & Klann, E. The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus. J. Neurosci., 2000(20): 3057-3066.
[127]. Chandler, L.J., Sutton, G., Dorairaj, N.R. & Norwood, D. N-methyl Daspartate receptor-mediated bidirectional control of extracellular signalregulated kinase activity in cortical neuronal cultures. J. Biol. Chem., 2001(276): 2627-2636.
[128]. Koob G.F., Sanna P.P. Bloom F.E. Neuroscience of addiction. Neuron, 1998(21): 467-476.
[129]. Levine, G.H., Maglio, J.J.& Horwitz, J. Differential effects of ethanol on signal transduction. Alcohol Clin. Exp. Res., 2000(24): 93-101.
[130]. Sanna, P.P., Simpson, C., Lutjens, R. & Koob, G. ERK regulation in chronic ethanol exposure and withdrawal. Brain Res., 2002(948), 186-191.
[131]. Kalluri, H.S.G. & Ticku, M.J. Ethanol-mediated inhibition of MAP kinase phosphorylation: role of calcium calmodulin dependent protein kinase. Alcohol Clin. Exp. Res., 2000b( Suppl., 24), 119.
[132]. Kalluri, H.S. & Ticku, M.K. Ethanol-mediated inhibition of mitogenactivated protein kinase phosphorylation in mouse brain. Eur. J. Pharmacol., 2002(439), 53-58.
[133]. Steven E. Hyman, Robert C. Malenka, and Eric J. Nestler. Neural Mechanisms of Addiction: The Role of Reward-Related Learning and Memory Annu. Rev. Neurosci. 2006(29): 565-598
[134]. Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP.Limbic activation during cue-induced cocaine craving. Am. J. Psychiatry 1999(156): 11-18
[135]. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci. 2005(8): 1481-89
[136]. Vanderschuren LJ, Everitt BJ. Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 2004(305): 1017-19
[137]. Dong Y, Nasif FJ, Tsui JJ, Ju WY, Cooper DC, et al. Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: adaptations in potassium currents. J. Neurosci. 2005(25): 936-40
[138]. Pandey SC. The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction. Pharmacol. Ther. 2004(104): 47-58
[139]. Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb. Cortex 2000(10): 318-25
[140]. Hyman SE. Addiction: a disease of learning and memory. Am. J. Psychiatry 2005.162(8): 1414-22
[141]. Hyman SE, Malenka RC. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. Neurosci. 2001(2): 695-703
[142]. Xia JX, Zhou R, Li jing, Yuan XR. Alterations of Rat Corticostriatal Synaptic Plasticity After Chronic Ethanol Exposure and Withdrawal. Alcoholism:Clinical and Experimental Research, 2006.30(5): 819-824
[143]. Arvind Kumar, Kwang-Ho Choi, William Renthal. et al. Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum. Neuron, 2005(48), 303-314
[144]. Costello D.A., Herron C.E. The role of c-Jun N-terminal kinase in the Aβ-mediated impairment of LTP and regulation of synaptic transmission in the hippocampus. Neuropharmacology. 2004(46): 655-662
[145]. Li X.M., Li C.C, Yu S.S., et al. JNK1 contributes to metabotropic glutamatereceptor-dependent long-term depression and short-term synaptic plasticity in the mice area hippocampal CA1. Europ J. of Neurosci. 2007(25): 391-396
[146]. Wang Q.W, Walsh D.M, Rowan M.J. et al. Involvement of JNK, Cdk5, p38 MAPK, and mGluR5 in AβBlock of LTP. J. Neurosci., 2004.24(13):370-378
[147]. Robbins TW, Ersche KD, Everitt BJ. Drug addiction and the memory systems of the brain. Ann N Y Acad Sci. 2008(1141): 1-21.
[1]. Cami J, Fare M. Drug addiction. N Engl J Med , 2003(349): 975-86.
[2]. Hyman, S.E., Malenka, R.C., Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. Neurosci. 2001(2): 695-703.
[3]. Kelley AE, Berridge KC. The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci , 2002 (22): 3306 - 3311
[4]. Thomas, M.J., Beurrier, C., Bonci, A., Malenka, R.C., Longterm depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-1223.
[5]. Lisman, J.E., Otmakhova, N.A.. Storage, recall, and novelty detection ofsequences by the hippocampus: elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine. Hippocampus, 2001(11): 551-568.
[6]. Jay, T.M.. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog. Neurobiol. , 2003(69): 375-390.
[7]. Fagen, Z.M., Mansvelder, H.D., Keath, J.R., McGehee, D.S. Short- and long-term modulation of synaptic inputs to brain reward areas by nicotine. Ann. N. Y. Acad. Sci. 2003(1003): 185-195.
[8]. Lovinger D.M., Partridge J.G., Tang K.C. Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse. Ann. N. Y.Acad. Sci. 2003(1003): 226-240.
[9]. Robbe, D., Alonso, G., Manzoni, O.J. Exogenous and endogenous cannabinoids control synaptic transmission in mice nucleus accumbens. Ann. N. Y. Acad. Sci. 2003(1003): 2121-2225.
[10]. Siggins, G.R., Martin, G., Roberto, M., Nie, Z., Madamba, S., De Lecea, L., Glutamatergic transmission in opiate and alcohol dependence. Ann. N. Y. Acad. Sci. 2003(1003): 196-2001.
[11]. Woodward, J.J., Ethanol and NMDA receptor signaling. Crit.Rev. Neurobiol. 2000(14): 69-89
[12]. Paulson, P.E., Camp, D.M., Robinson, T.E., Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats. Psychopharmacology 1991(103): 480-492.
[13]. Vezina, P., Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs.Neurosci. Biobehav. Rev. 2004(27): 827-839.
[14]. Ungless, M.A., Whistler, J.L., Malenka, R.C., Bonci, A., Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 2001(411): 583-587.
[15]. Schultz, W., Getting formal with dopamine and reward. Neuron 2002(36): 241-263.
[16]. Saal, D., Dong, Y., Bonci, A., Malenka, R.C., Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 2003(37): 577-582.
[17]. Vanderschuren, L.J.M.J., Schmidt, E.D., De Vries, T.J., Van Moorsel, C.A.P., Tilders, F.J.H., Schoffelmeer, A.N.M., A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization. J.Neurosci. 1999(19): 9579-9586.
[18]. Thomas, M.J., Malenka, R.C., Bonci, A., Modulation of long term depression by dopamine in the mesolimbic system. J. Neurosci. 2000(20): 5581-5586.
[19]. Wolf, M.E., Addiction and glutamate-dependent plasticity. In: Herman, B.H., Frankenheim, J., Litten, R., Sheridan, P.H.,Weight, F.F., Zukin, S.R. (Eds.), Glutamate and Addiction. Humana Press, Totowa, NJ, 2002: 127-142.
[20]. Kelley, A.E., Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci.Biobehav. Rev. 2004(27): 765-776.
[21]. Wang, X., Zhong, P., Gu, Z., Yan, Z., Regulation of NMDAreceptors by dopamine D4 signaling in prefrontal cortex. J. Neurosci. 2003(23): 9852-9861.
[22]. Otani, S., Daniel, H., Roisin, M.P., Crepel, F., Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons.Cereb. Cortex 2003(13): 1251-1256.
[23]. Blond, O., Crepel, F., Otani, S., Long-term potentiation in rat prefrontal slices facilitated by phased application of dopamine.Eur. J. Pharmacol. 2002(438): 115-116.
[24]. Huang, Y.-Y., Simpson, E., Kellendonk, C., Kandel, E.R., Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc. Natl. Acad. Sci. 2004(101): 3236-3241.
[25]. Gurden, H., Tassin, J.P., Jay, T.M., Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation. Neuroscience 1999(94): 1019-1027.
[26]. Peterson, J.D., Wolf, M.E., White, F.J., Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment. Synapse 2000(36): 342-344.
[27]. Dong Y, Nasif FJ, Tsui JJ, Ju WY, Cooper DC, et al. Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: adaptations in potassium currents. J. Neurosci. 2005(25): 936-40
[28]. Kalivas, P.W., McFarland, K., Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 2003(168): 45-56.
[29]. Li, Y., Kauer, J.A., Repeated exposure to amphetamine disrupts dopaminergic modulation of excitatory synaptic plasticity and neurotransmission in the nucleus accumbens. Synapse 2004(51): 1-10
[30]. Thomas, M.J., Beurrier, C., Bonci, A., Malenka, R.C., Long term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-1223.
[31]. Robbe, D., Alonso, G., Chaumont, S., Bockaert, J., Manzoni, O.J., Role of P/Q-Ca2+ channels in metabotropic glutamate receptor 2/3 dependent presynaptic long-term depression at nucleus accumbens synapses. J. Neurosci. 2002(22): 4346-4356.
[32]. Wolf, M.E., Addiction and glutamate-dependent plasticity. In: Herman, B.H., Frankenheim, J., Litten, R., Sheridan, P.H., Weight, F.F., Zukin, S.R. (Eds.), Glutamate and Addiction. Humana Press, Totowa, NJ, 2002: 127-142.
[33]. Beurrier C, Malenka RC. Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine. J. Neurosci. 2002(22): 5817-22
[34]. Li Y, Kauer JA. Repeated exposure to amphetamine disrupts dopaminergicmodulation of excitatory synaptic plasticity and neurotransmission in nucleus accumbens. Synapse 2004(51):1-10
[35]. Hoffman AF, Oz M, Caulder T, Lupica CR. Functional tolerance and blockade of long term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. J. Neurosci. 2003(23): 4815-20
[36]. Lovinger, D.M., Partridge, J.G., Tang, K.-C., Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse. Ann. N. Y.Acad. Sci. 2003(1003): 226-240.
[37]. Dunah, A.W., Standaert, D.G., Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. J. Neurosci. 2001(21): 5546-5558.
[38]. Bibb, J.A., Chen, J., Taylor, J.R., Svenningsson, P., Nishi, A., Snyder, G.L., Yan, Z., Sagawa, Z.K., Ouimet, C.C., Nairn, A.C., Nestler, E.J., Greengard, P., Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001(410): 376-380.
[12]. Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J. Neural systems and cue-induced cocaine craving. Neuropsychopharmacology, 2002 (26): 376-86
[13]. Kelley AE, Berridge KC. The neuroscience of natural rewards: relevance to addictive drugs. J. Neurosci. 2002(22): 3306-11
[14]. Berke JD, Sgambato V, Zhu P-P, Lavoie B, Vincent M. Dopamine and glutamate induce distinct striatal splice forms of ania-6, an RNA polymerase II-associated cyclin. Neuron . 2001 (32): 1-20
[15]. Everitt BJ, Dickinson A, Robbins TW. The neuropsychological basis of addictive behaviour. Brain Res. Brain Res. Rev. 2001, 36 (2-3):129-138
[16]. Paulus MP, Tapert SF, Schuckit MA. Neural activation patterns of methamphetaminedependent subjects during decision making predict relapse. Arch. Gen. Psychiatry, 2005, 62(7): 761-768
[17]. Robinson S, Sandstrom SM, Denenberg VH, Palmiter RD. Distinguishing whether dopamine regulates liking, wanting, and/or learning about rewards. Behav. Neurosci. 2005(199): 336-341
[18]. Bayer HM, Glimcher PW. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron, 2005, 47(1): 129-141
[19]. Semenova S, Markou A. Cocaine-seeking behavior after extended cocaine-free periods in rats: role of conditioned stimuli. Psychopharmacology, 2003(168): 192-200
[20]. Borgland SL, Malenka RC, Bonci A. Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: electrophysiological and behavioral correlates in individual rats. J. Neurosci. 2004(24): 7482-490
[21]. Everitt BJ, Wolf ME. Psychomotor stimulant addiction: a neural systems perspective. J. Neurosci. 2002, 22(9): 3312-20
[22]. Hnasko TS, Sotak BN, Palmiter RD. Morphine reward in dopamine-deficientmice. Nature 2005(438): 854-57
[23]. Kringelbach ML. The human orbitofrontal cortex: linking reward to hedonic experience. Nat. Rev. Neurosci. 2005, 6(9): 691-702
[24]. Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry , 2002(159): 1642-52
[25]. Gottfried JA, O’Doherty J, Dolan RJ. Encoding predictive reward value in human amygdale and orbitofrontal cortex. Science, 2003(301): 1104-7
[26]. Faleiro LJ, Jones S, Kauer JA. Rapid synaptic plasticity of glutamatergic synapses on dopamine neurons in the ventral tegmental area in response to acute amphetamine injection. Neuropsychopharmacology, 2004(29): 2115-25
[27]. Harris GC, Aston-Jones G. Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment. Neuropsychopharmacology, 2003(28): 73-76
[28]. Kauer JA. Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu. Rev. Physiol. 2004(66): 447-75
[29]. Kalivas PW, Volkow N, Seamans J. Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron. 2005(45): 647-50
[30]. Everitt BJ, Cardinal RN, Parkinson JA, Robbins TW. Appetitive behavior: impact of amygdala-dependent mechanisms of emotional learning. Ann. N. Y. Acad. Sci. 2003(985): 233-50
[31]. Dumont EC, Mark GP, Mader S, Williams JT. Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis. Nat. Neurosci. 2005(8): 413-14
[32]. Deroche-Gamonet V, Belin D, Piazza PV. Evidence for addiction-like behavior in the rat. Science. 2004(305): 1014-17
[33]. Carlezon WA Jr, Nestler EJ. Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse? Trends Neurosci. 2002(25): 610-15
[34]. Cannon CM, Palmiter RD. Reward without dopamine. J. Neurosci. 2003(23): 10827-31
[35]. Di Chiara G. A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use. J. Psychopharmacol. 1998(12): 54-67
[36]. Kumar A, Choi K-H, Renthal W, Tsankova NM, Theobald DEH. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron. 2005(48): 303-14
[37]. Matsumoto K, Suzuki W, Tanaka K. Neuronal correlates of goal-based motor selection in the prefrontal cortex. Science. 2003(301): 229-32
[38]. Yin, H.H. & Knowlton, B.J. Contributions of striatal subregions to place and response learning. Learn. Mem., 2004(11) : 459-463.
[39]. Yin, H.H. & Knowlton, B.J. The role of the basal ganglia in habit formation. Nature Rev. Neurosci. 2006(7): 464-476.
[40]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning. Eur. J. Neurosci., 2004(19): 181-189.
[41]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning. Eur. J. Neurosci., 2005a(22): 505-512.
[42]. Yin, H.H., Knowlton, B.J. & Balleine, B.W. Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning. Behav. Brain Res., 2006(166): 189-196.
[43]. Yin, H.H., Ostlund, S.B., Knowlton, B.J. & Balleine, B.W. The role of the dorsomedial striatum in instrumental conditioning. Eur. J. Neurosci., 2005b(22): 513-523
[44]. Chklovskii DB, Mel BW, Svoboda K. Cortical rewiring and information storage.Nature, 2004(431): 782-88
[45]. Choi KH, Rahman Z, Edwards S, Hall S, Neve RL, Self DW. Opposite effects of GluR1 and PKA-resistant GluR1 overexpression in the ventral tegmental area on cocaine reinforcement. Ann. N. Y. Acad. Sci. 2003(1003): 372-74
[46]. Barnes TD, Kubota Y, Hu D, Jon DZ, Graybiel AM. Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories. Nature 2005(437): 1158-61
[47]. Atallah, H.E., Lopez-Paniagua, D., Rudy, J.W. & O’Reilly, R.C. Separate neural substrates for skill learning and performance in the ventral and dorsal striatum. Nature Neurosci., 2007(10): 126-131
[48]. Bailey, K.R. & Mair, R.G. The role of striatum in initiation and execution of learned action sequences in rats. J. Neurosci., 2006 (26): 1016-1025
[49]. Brebner K, Wong TP, Liu L, Liu Y, Campsall P. Nucleus accumbens long-term depression and the expression of behavioral sensitization. Science 2005 (310): 1340-43
[50]. Bliss, T.V.P. & Collingridge, G.L. A synaptic model of memory: longterm potentiation in the hippocampus. Nature, 1993(361): 31-39.
[51]. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron, 2004(44): 5-21
[52]. Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 2000(23): 649-711
[53]. Welsby PJ, Rowan MJ, Anwyl R. Intracellular mechanisms underlying the nicotinic enhancement of LTP in the rat dentate gyrus. Eur J Neurosci. 2009, 29(1):65-75.
[54]. Kalivas PW. Glutamate systems in cocaine addiction. Curr. Opin. Pharmacol. 2004(4): 23-29
[55]. Szumlinski KK, Dehoff MH, Kang SH. Homer proteins regulate sensitivity to cocaine. Neuron. 2004(43): 401-13
[56]. Hope B, Kosofsky B, Hyman SE, Nestler EJ. Regulation of IEG expression and AP-1 binding by chronic cocaine in the rat nucleus accumbens. Proc. Natl. Acad. Sci. USA, 1992(89): 5764-68
[57]. Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat. Rev. Genet. 2005(6): 521-32
[58]. Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW. Striatal cell type-specific overexpression of FosB enhances incentive for cocaine. J. Neurosci. 2003, 23(6): 2488-93
[59]. Daunais JB, McGinty JF. Acute and chronic cocaine administration differentially alters striatal opioid and nuclear transcription factor mRNAs. Synapse, 1994(18): 35-46
[60]. Chao J, Nestler EJ. Molecular neurobiology of drug addiction. Annu. Rev. Med. 2004(55): 113-32
[61]. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS. Defining the CREB regulon: a genome-wide analysis of transcription factor regulator regions. Cell, 2004(119): 1041-54
[62]. McClung CA, Nestler EJ. Regulation of gene expression and cocaine reward by CREB and FosB. Nat. Neurosci. 2003(6): 1208-15
[63]. Kelz MB, Chen JS, Carlezon WA Jr, Whisler K, Gilden L. Expression of the transcription factor FosB in the brain controls sensitivity to cocaine. Nature 1999(401): 272-76
[64]. Olson VG, Zabetian CP, Bolanos CA, Edwards S, Barrot M, et al. Regulation of drug reward byCREB:evidence for two functionally distinct subregions of the ventral tegmental area. J. Neurosci. 2005(25): 5553-62
[65]. Carlezon WA Jr, Duman RS, Nestler EJ. The many faces of CREB. Trends Neurosci. 2005(28): 436-45
[66]. Brunzell DH, Russell DS, Picciotto MR. In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice. J. Neurochem.2003(84): 1431-41
[67]. Zhang X, OdomDT, Koo SH, Conkright MD, Canettieri G. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc. Natl. Acad. Sci. 2005, 102(12): 4459-64
[68]. Walters CL, Kuo YC, Blendy JA. Differential distribution of CREB in the mesolimbic dopamine reward pathway. J. Neurochem. 2003(87): 1237-44
[69]. Roberson, E.D., English, J.D., Adams, J.P., Selcher, J.C., Kondratick, C. & Sweatt, J.D. The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus. J. Neurosci., 1999(19): 4337-4348.
[70]. Huang YH, Lin Y, Brown TE, Han MH, Saal DB, Neve RL, Zukin RS, Sorg BA, Nestler EJ, Malenka RC, Dong Y. CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors. J Biol Chem. 2008, 283 (5): 2751-60
[71]. Konradi C, Leveque JC, Hyman SE. Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium. J. Neurosci. 1996(16): 4231-39
[72]. Shaw-Lutchman TZ, Impey S, Storm D, Nestler EJ. Regulation of CRE-mediated transcription in mouse brain by amphetamine. Synapse, 2003(48): 10-17
[73]. Walters CL, Cleck JN, Kuo YC, Blendy JA.μ-opioid receptor and CREB activation are required for nicotine reward. Neuron, 2005(16): 933-43
[74]. Zachariou V, Bolanos CA, Selley DE, Theobald D, Cassidy MP, et al. FosB: an essential role for FosB in the nucleus accumbens in morphine action. Nat. Neurosci. 2006(9): 205-11
[75]. Boulton, T.G., Nye, S.H., Robbins, D.J., Ip, N.Y., Radziejewska, E., Morgenbesser, S.D., DePinho, R.A., Panayotatos, N., Cobb, M.H. &Yancopoulos, G.D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell, 1991(65): 663-675.
[76]. Blum, S., Moore, A.N., Adams, F. & Dash, P.K. A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory. J. Neurosci., 1999(19): 3535-3544.
[77]. Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev., 2000(80): 953-978.
[78]. Barrot M, Olivier JDA, Perrotti LI, Impey S, Storm DR, et al. CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Proc. Natl. Acad. Sci. 2002(99): 11435-40
[79]. Ito R, Robbins TW, Everitt BJ. Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat. Neurosci. 2004, 7(4): 389-97
[80]. Packard MG, Knowlton BJ. Learning and memory functions of the basal ganglia. Annu. Rev. Neurosci. 2002(25): 563-93
[81]. White, N.M. Mnemonic functions of the basal ganglia. Curr. Opin. Neurobiol., 1997(7): 164-169.
[82]. Partridge, J.G., Tang, K.C. & Lovinger, D.M. Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum. J. Neurophysiol., 2000(84): 1422-1429.
[83]. Nicoll, R.A. Expression mechanisms underlying long-term potentiation: a postsynaptic view. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2003(358): 721-726.
[84]. Kreitzer A, Malenka RC. Dopamine modulation of state-dependent endocannabinoid release and LTD in the striatum. J. Neurosci. 2005(25): 10537-45
[85]. Kombian SB, Malenka RC. Simultaneous LTP of non-NMDA- and LTD ofNMDAreceptor- mediated responses in the nucleus accumbens. Nature. 1994(368): 242-46
[86]. McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ. FosB: a molecular switch for long-term adaptation. Mol. Brain Res. 2004(132): 146-54
[87]. Cunningham, C.L., Howard, M.A., Gill, S.J., Rubinstein, M., Low, M.J. & Grandy, D.K. Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice. Pharmacol. Biochem. Behav., 2000(67): 693-699.
[88]. Dang, M.T., Yokoi, F., Yin, H.H., Lovinger, D.M., Wang, Y. & Li, Y. Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum. Proc. Natl Acad. Sci. 2006(103): 15254-15259.
[89]. Reynolds, J.N., Hyland, B.I. & Wickens, J.R. A cellular mechanism of reward-related learning. Nature, 2001(413): 67-70.
[90]. Kobayashi, T., Ikeda, K., Kojima, H., Niki, H., Yano, R., Yoshioka, T. & Kumanishi, T. Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nature Neurosci., 1999(2): 1091-1097.
[91]. Lovinger, D.M., White, G. & Weight, F.F. Ethanol inhibits NMDAactivated ion current in hippocampal neurons. Science, 1989(243): 1721-1724.
[92]. Lovinger, D.M. Alcohols and neurotransmitter gated ion channels: past, present and future. Naunyn Schmiedebergs Arch. Pharmacol., 1997(356): 267-282.
[93]. Schultz W. Behavioral theories and the neurophysiology of reward. Annu. Rev. Psychol. 2006(57): 87-11
[94]. Self DW. Regulation of drug-taking and -seeking behaviors by neuroadaptations in the mesolimbic dopamine system. Neuropharmacology, 2004(47, Suppl. 1): 242-55
[95]. Schummers J., Bentz S. Browning, M.D. Ethanol’s inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor. Alcohol Clin. Exp. Res., 1997(21): 404-408.
[96]. Morrisett, R.A. & Swartzwelder, H.S. Attenuation of hippocampal longtermpotentiation by ethanol: a patch-clamp analysis of glutamatergic and GABAergic mechanisms. J. Neurosci., 1993(13): 2264-2272.
[97]. Henry H. Yin, Brian S. Park, Louise Adermark and David M. Lovinger. Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum European Journal of Neuroscience, 2007(25): 3226-3232
[98]. Izumi, Y., Nagashima, K., Murayama, K. & Zorumski, C.F. Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms. Neuroscience, 2005a(136): 509-517.
[99]. Thomas MJ, Beurrier C, Bonci A, Malenka RC. Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-23
[100]. Wang, Z., Kai, L., Day, M., Ronesi, J., Yin, H.H., Ding, J., Tkatch, T., Lovinger, D.M. & Surmeier, D.J. Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron, 2006(50): 443-452.
[101]. Kerr, J.N. & Wickens, J.R. Dopamine D-1 ? D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro. J. Neurophysiol., 2001(85): 117-124.
[102]. Calabresi, P., Maj, R., Pisani, A., Mercuri, N.B. & Bernardi, G. Longterm synaptic depression in the striatum: physiological and pharmacological characterization. J. Neurosci., 1992(12): 4224-4233.
[103]. Piomelli, D. The molecular logic of endocannabinoid signalling. Nature Rev. Neurosci., 2003(4): 873-884.
[104]. Ronesi, J., Gerdeman, G.L. & Lovinger, D.M. Disruption of endocannabinoid release and striatal long-term depression by postsynapticblockade of endocannabinoid membrane transport. J. Neurosci., 2004(24): 1673-1679.
[105]. Gerdeman, G.L., Ronesi, J. & Lovinger, D.M. Postsynaptic endocannabinoids release is critical to long-term depression in the striatum. Nature Neurosci.,2002(5): 446-451.
[106]. Giuffrida, A., Parsons, L.H., Kerr, T.M., Rodriguez de Fonseca, F., Navarro, M. & Piomelli, D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature Neurosci., 1999(2): 358-363.
[107]. Kreitzer, A.C. & Malenka, R.C. Dopamine modulation of statedependent endocannabinoid release and long-term depression in the striatum. J. Neurosci., 2005(25): 10537-10545.
[108]. Schummers, J., Bentz, S. & Browning, M.D. Ethanol’s inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor. Alcohol Clin. Exp. Res., 1997(21): 404-408.
[109]. Adams, J.P. & Sweatt, J.D. Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol., 2002(42): 135-163.
[110]. Atkins, C.M., Selcher, J.C., Petraitis, J.J., Trzaskos, J.M. & Sweatt, J.D. The MAPK cascade is required for mammalian associative learning. Nature Neurosci., 1998(1): 602-609.
[111]. Kornhauser, J.M. & Greenberg, M.E. A kinase to remember: dual roles for MAP kinase in long-term memory. Neuron, 1997(18): 839-842.
[112]. Sweatt, J.D. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J. Neurochem., 2001(76): 1-10.
[113]. M. Roberto, T. E. Nelson, C. L. Ur, 1 M. Brunelli, P. P. Sanna1 and D. L. Gruol1.The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway European Journal of Neuroscience, 2003(17): 1646-1654
[114]. John M. Schmitt, Gary A. Wayman, Naohito Nozaki, and Thomas R. Soderling Calcium Activation of ERK Mediated by Calmodulin Kinase I The Journal Of Biological Chemistry, 2004. 279(23): 24064-24072
[115]. English, J.D. Sweatt, J.D. Activation of p42 mitogen-activated protein kinasein hippocampal long term potentiation. J. Biol. Chem., 1996(271): 24329-24332.
[116]. English, J.D. Sweatt, J.D. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J. Biol. Chem., 1997(272): 19103-19106.
[117]. Rosenblum, K., Futter, M., Voss, K., Erent, M., Skehel, P.A., French, P., Obosi, L., Jones, M.W. & Bliss, T.V. The role of extracellular regulated kinases I/II in late-phase long-term potentiation. J. Neurosci., 2002(22): 5432-5441.
[118]. Winder, D.G., Martin, K.C., Muzzio, I.A., Rohrer, D., Chruscinski, A., Kobilka, B. & Kandel, E.R. ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors. Neuron, 1999(24): 715-726.
[119]. Wu S.P., Lu, K.T., Chang W.C. & Gean P.W. Involvement of mitogenactivated protein kinase in hippocampal long-term potentiation. J. Biomed. Sci., 1999(6): 409-417.
[120]. Cui Y, Costa RM, Murphy GG, et al . Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell. 2008,135(3): 549-60.
[121]. Toyoda H, Zhao MG, Xu H, Wu LJ, Ren M, Zhuo M. Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex. Mol Pain. 2007(3): 36.
[122]. Roberto, M., Nelson, T.E., Ur, C.L. & Gruol, D.L. Long-term potentiation in the rat hippocampus is reversibly depressed by chronic intermittent ethanol exposure. J. Neurophysiol., 2002(87): 2385-2397.
[123]. Rosen, L.B., Ginty, D.D., Weber, M.J. Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras. Neuron, 1994(12): 1207-1221.
[124]. Rosenblum, K., Futter, M., Jones, M., Hulme, E.C.& Bliss, T.V. ERKI/II regulation by the muscarinic acetylcholine receptors in neurons. J. Neurosci.,2000(20): 977-985.
[125]. Soderling, T.R., Chang, B. & Brickey, D. Cellular signaling through multifunctional Ca2t/calmodulin-dependent protein kinase II. J. Biol. Chem., 2001(276): 3719-3722.
[126]. Kanterewicz, B.I., Urban, N.N., McMahon, D.B., Norman, E.D., Giffen, L.J., Favata, M.F., Scherle, P.A., Trzskos, J.M., Barrionuevo, G. & Klann, E. The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus. J. Neurosci., 2000(20): 3057-3066.
[127]. Chandler, L.J., Sutton, G., Dorairaj, N.R. & Norwood, D. N-methyl Daspartate receptor-mediated bidirectional control of extracellular signalregulated kinase activity in cortical neuronal cultures. J. Biol. Chem., 2001(276): 2627-2636.
[128]. Koob G.F., Sanna P.P. Bloom F.E. Neuroscience of addiction. Neuron, 1998(21): 467-476.
[129]. Levine, G.H., Maglio, J.J.& Horwitz, J. Differential effects of ethanol on signal transduction. Alcohol Clin. Exp. Res., 2000(24): 93-101.
[130]. Sanna, P.P., Simpson, C., Lutjens, R. & Koob, G. ERK regulation in chronic ethanol exposure and withdrawal. Brain Res., 2002(948), 186-191.
[131]. Kalluri, H.S.G. & Ticku, M.J. Ethanol-mediated inhibition of MAP kinase phosphorylation: role of calcium calmodulin dependent protein kinase. Alcohol Clin. Exp. Res., 2000b( Suppl., 24), 119.
[132]. Kalluri, H.S. & Ticku, M.K. Ethanol-mediated inhibition of mitogenactivated protein kinase phosphorylation in mouse brain. Eur. J. Pharmacol., 2002(439), 53-58.
[133]. Steven E. Hyman, Robert C. Malenka, and Eric J. Nestler. Neural Mechanisms of Addiction: The Role of Reward-Related Learning and Memory Annu. Rev. Neurosci. 2006(29): 565-598
[134]. Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP.Limbic activation during cue-induced cocaine craving. Am. J. Psychiatry 1999(156): 11-18
[135]. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci. 2005(8): 1481-89
[136]. Vanderschuren LJ, Everitt BJ. Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 2004(305): 1017-19
[137]. Dong Y, Nasif FJ, Tsui JJ, Ju WY, Cooper DC, et al. Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: adaptations in potassium currents. J. Neurosci. 2005(25): 936-40
[138]. Pandey SC. The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction. Pharmacol. Ther. 2004(104): 47-58
[139]. Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb. Cortex 2000(10): 318-25
[140]. Hyman SE. Addiction: a disease of learning and memory. Am. J. Psychiatry 2005.162(8): 1414-22
[141]. Hyman SE, Malenka RC. Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. Neurosci. 2001(2): 695-703
[142]. Xia JX, Zhou R, Li jing, Yuan XR. Alterations of Rat Corticostriatal Synaptic Plasticity After Chronic Ethanol Exposure and Withdrawal. Alcoholism:Clinical and Experimental Research, 2006.30(5): 819-824
[143]. Arvind Kumar, Kwang-Ho Choi, William Renthal. et al. Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum. Neuron, 2005(48), 303-314
[144]. Costello D.A., Herron C.E. The role of c-Jun N-terminal kinase in the Aβ-mediated impairment of LTP and regulation of synaptic transmission in the hippocampus. Neuropharmacology. 2004(46): 655-662
[145]. Li X.M., Li C.C, Yu S.S., et al. JNK1 contributes to metabotropic glutamatereceptor-dependent long-term depression and short-term synaptic plasticity in the mice area hippocampal CA1. Europ J. of Neurosci. 2007(25): 391-396
[146]. Wang Q.W, Walsh D.M, Rowan M.J. et al. Involvement of JNK, Cdk5, p38 MAPK, and mGluR5 in AβBlock of LTP. J. Neurosci., 2004.24(13):370-378
[147]. Robbins TW, Ersche KD, Everitt BJ. Drug addiction and the memory systems of the brain. Ann N Y Acad Sci. 2008(1141): 1-21.
[1]. Cami J, Fare M. Drug addiction. N Engl J Med , 2003(349): 975-86.
[2]. Hyman, S.E., Malenka, R.C., Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. Neurosci. 2001(2): 695-703.
[3]. Kelley AE, Berridge KC. The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci , 2002 (22): 3306 - 3311
[4]. Thomas, M.J., Beurrier, C., Bonci, A., Malenka, R.C., Longterm depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-1223.
[5]. Lisman, J.E., Otmakhova, N.A.. Storage, recall, and novelty detection ofsequences by the hippocampus: elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine. Hippocampus, 2001(11): 551-568.
[6]. Jay, T.M.. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog. Neurobiol. , 2003(69): 375-390.
[7]. Fagen, Z.M., Mansvelder, H.D., Keath, J.R., McGehee, D.S. Short- and long-term modulation of synaptic inputs to brain reward areas by nicotine. Ann. N. Y. Acad. Sci. 2003(1003): 185-195.
[8]. Lovinger D.M., Partridge J.G., Tang K.C. Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse. Ann. N. Y.Acad. Sci. 2003(1003): 226-240.
[9]. Robbe, D., Alonso, G., Manzoni, O.J. Exogenous and endogenous cannabinoids control synaptic transmission in mice nucleus accumbens. Ann. N. Y. Acad. Sci. 2003(1003): 2121-2225.
[10]. Siggins, G.R., Martin, G., Roberto, M., Nie, Z., Madamba, S., De Lecea, L., Glutamatergic transmission in opiate and alcohol dependence. Ann. N. Y. Acad. Sci. 2003(1003): 196-2001.
[11]. Woodward, J.J., Ethanol and NMDA receptor signaling. Crit.Rev. Neurobiol. 2000(14): 69-89
[12]. Paulson, P.E., Camp, D.M., Robinson, T.E., Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats. Psychopharmacology 1991(103): 480-492.
[13]. Vezina, P., Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs.Neurosci. Biobehav. Rev. 2004(27): 827-839.
[14]. Ungless, M.A., Whistler, J.L., Malenka, R.C., Bonci, A., Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 2001(411): 583-587.
[15]. Schultz, W., Getting formal with dopamine and reward. Neuron 2002(36): 241-263.
[16]. Saal, D., Dong, Y., Bonci, A., Malenka, R.C., Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 2003(37): 577-582.
[17]. Vanderschuren, L.J.M.J., Schmidt, E.D., De Vries, T.J., Van Moorsel, C.A.P., Tilders, F.J.H., Schoffelmeer, A.N.M., A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization. J.Neurosci. 1999(19): 9579-9586.
[18]. Thomas, M.J., Malenka, R.C., Bonci, A., Modulation of long term depression by dopamine in the mesolimbic system. J. Neurosci. 2000(20): 5581-5586.
[19]. Wolf, M.E., Addiction and glutamate-dependent plasticity. In: Herman, B.H., Frankenheim, J., Litten, R., Sheridan, P.H.,Weight, F.F., Zukin, S.R. (Eds.), Glutamate and Addiction. Humana Press, Totowa, NJ, 2002: 127-142.
[20]. Kelley, A.E., Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci.Biobehav. Rev. 2004(27): 765-776.
[21]. Wang, X., Zhong, P., Gu, Z., Yan, Z., Regulation of NMDAreceptors by dopamine D4 signaling in prefrontal cortex. J. Neurosci. 2003(23): 9852-9861.
[22]. Otani, S., Daniel, H., Roisin, M.P., Crepel, F., Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons.Cereb. Cortex 2003(13): 1251-1256.
[23]. Blond, O., Crepel, F., Otani, S., Long-term potentiation in rat prefrontal slices facilitated by phased application of dopamine.Eur. J. Pharmacol. 2002(438): 115-116.
[24]. Huang, Y.-Y., Simpson, E., Kellendonk, C., Kandel, E.R., Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors. Proc. Natl. Acad. Sci. 2004(101): 3236-3241.
[25]. Gurden, H., Tassin, J.P., Jay, T.M., Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation. Neuroscience 1999(94): 1019-1027.
[26]. Peterson, J.D., Wolf, M.E., White, F.J., Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment. Synapse 2000(36): 342-344.
[27]. Dong Y, Nasif FJ, Tsui JJ, Ju WY, Cooper DC, et al. Cocaine-induced plasticity of intrinsic membrane properties in prefrontal cortex pyramidal neurons: adaptations in potassium currents. J. Neurosci. 2005(25): 936-40
[28]. Kalivas, P.W., McFarland, K., Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 2003(168): 45-56.
[29]. Li, Y., Kauer, J.A., Repeated exposure to amphetamine disrupts dopaminergic modulation of excitatory synaptic plasticity and neurotransmission in the nucleus accumbens. Synapse 2004(51): 1-10
[30]. Thomas, M.J., Beurrier, C., Bonci, A., Malenka, R.C., Long term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 2001(4): 1217-1223.
[31]. Robbe, D., Alonso, G., Chaumont, S., Bockaert, J., Manzoni, O.J., Role of P/Q-Ca2+ channels in metabotropic glutamate receptor 2/3 dependent presynaptic long-term depression at nucleus accumbens synapses. J. Neurosci. 2002(22): 4346-4356.
[32]. Wolf, M.E., Addiction and glutamate-dependent plasticity. In: Herman, B.H., Frankenheim, J., Litten, R., Sheridan, P.H., Weight, F.F., Zukin, S.R. (Eds.), Glutamate and Addiction. Humana Press, Totowa, NJ, 2002: 127-142.
[33]. Beurrier C, Malenka RC. Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine. J. Neurosci. 2002(22): 5817-22
[34]. Li Y, Kauer JA. Repeated exposure to amphetamine disrupts dopaminergicmodulation of excitatory synaptic plasticity and neurotransmission in nucleus accumbens. Synapse 2004(51):1-10
[35]. Hoffman AF, Oz M, Caulder T, Lupica CR. Functional tolerance and blockade of long term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. J. Neurosci. 2003(23): 4815-20
[36]. Lovinger, D.M., Partridge, J.G., Tang, K.-C., Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse. Ann. N. Y.Acad. Sci. 2003(1003): 226-240.
[37]. Dunah, A.W., Standaert, D.G., Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. J. Neurosci. 2001(21): 5546-5558.
[38]. Bibb, J.A., Chen, J., Taylor, J.R., Svenningsson, P., Nishi, A., Snyder, G.L., Yan, Z., Sagawa, Z.K., Ouimet, C.C., Nairn, A.C., Nestler, E.J., Greengard, P., Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001(410): 376-380.