Activation of alpha1-adrenoceptors enhances glutamate release onto ventral tegmental area dopamine cells

详细信息	查看全文 | 推荐本文 |

• 作者：M.C. Velá ; squez-Martinez^a ; ^b ; R. Vá ; zquez-Torres^a ; C.A. Jimé ; nez-Rivera^a ; ^{carlos.jimenez8@upr.edu}
• 关键词：伪1-ARs ; alpha1-adrenoreceptors ; ACSF ; artificial cerebrospinal fluid ; BNST ; bed nucleus of the stria terminalis ; CP ; creatine phosphate ; DIC ; differential interference contrast ; DA ; dopamine ; EPSCs ; excitatory postsynaptic currents ; IPSC&rsquo ; s ; inhibit
• 刊名：Neuroscience
• 出版年：2012
• 期刊代码：50_03064522
• 类别：neu
• 出版时间：2 August, 2012
• 卷：216
• 期：Complete
• 页码：18-30
• 文件大小：1098 K

摘要

The ventral tegmental area (VTA) plays an important role in reward and motivational processes that facilitate the development of drug addiction. Glutamatergic inputs into the VTA contribute to dopamine (DA) neuronal activation related to reward and response-initiating effects in drug abuse. Previous investigations indicate that alpha1-adrenoreceptors (伪1-ARs) are primarily localized at presynaptic elements in the ventral midbrain. Studies from several brain regions have shown that presynaptic 伪1-AR activation enhances glutamate release. Therefore, we hypothesized that glutamate released onto VTA-DA neurons is modulated by pre-synaptic 伪1-AR. Recordings were obtained from putative VTA-DA cells of male Sprague-Dawley rats (28-50 days postnatal) using voltage clamp techniques. Phenylephrine (10 渭M) and methoxamine (80 渭M), both 伪1-AR agonists, increased AMPA receptor-mediated excitatory postsynaptic currents鈥?(EPSCs) amplitude evoked by electrical stimulation of afferent fibers (p < 0.05). This effect was blocked by the 伪1-AR antagonist prazosin (1 渭M). Phenylephrine decreased the paired-pulse ratio (PPR) and increased spontaneous EPSCs鈥?frequencies but not their amplitudes suggesting a presynaptic locus of action. No changes in miniature EPSCs (0.5 渭M, tetrodotoxin [TTX]) were observed after phenylephrine鈥檚 application which suggests that 伪1-AR effect was action potential dependent. Normal extra- and intracellular Ca²⁺ concentration seems necessary for the 伪1-AR effect since phenylephrine in low Ca²⁺ artificial cerebrospinal fluid (ACSF) and depletion of intracellular Ca²⁺ stores with thapsigargin (10 渭M) failed to increase the AMPA EPSCs鈥?amplitude. Chelerythrine (1 渭M, protein kinase C (PKC) inhibitor) but not Rp-cAMPS (11 渭M, PKA inhibitor) blocked the 伪1-AR activation effect on AMPA EPSCs, indicating that a PKC intracellular pathway is required. These results demonstrated that presynaptic 伪1-AR activation modulates glutamatergic inputs that affect VTA-DA neuronal excitability. 伪1-AR action might be heterosynaptically localized at glutamatergic fibers terminating onto VTA-DA neurons. It is suggested that drug-induced changes in 伪1-AR could be part of the neuroadaptations occurring in the mesocorticolimbic circuitry during the addiction process.