Long-lasting increase in [³H]CP55,940 binding to CB1 receptors following cocaine self-administration and its withdrawal in rats

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• 作者：Przemys&#322 ; aw Adamczyk^a ; ^{adamczyk@if-pan.krakow.pl} ; Agata Faron-Gó ; recka^b ; Maciej Kuś ; mider^b ; Marta Dziedzicka-Wasylewska^b ; Mariusz Papp^c ; Ma&#322 ; gorzata Filip^a
• 关键词：Cocaine ; Self-administration ; CB1 receptor ; [3H]CP55 ; 940 ; Autoradiography ; Rats
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：27 April, 2012
• 卷：1451
• 期：Complete
• 页码：34-43
• 文件大小：1258 K

摘要

The present work has aimed on the neuroadaptive changes in CB1 receptor density that are evoked by self-administered cocaine use and subsequent withdrawal in rats. We employed a quantitative autoradiographic analysis using labeled [³H]CP55,940, a CB1 receptor agonist. To distinguish the passive pharmacological effects of cocaine from those related to motivation and the cognitive processes evoked by active cocaine self-administration, the 鈥測oked鈥?procedure was used. Our results demonstrate that repeated cocaine administration over 14 days induced up-regulation of CB1 receptors in the cortical and subcortical brain areas of animals who received cocaine, whether the cocaine was actively self-administered or received passively (the 鈥測oked鈥?control group) and that the neuroadaptation of CB1 receptors persisted after the 10-day extinction phase. On the other hand, we found that only self-administering rats showed CB1 receptor up-regulation in numerous brain areas, which suggests that these structures may be directly linked to CB1 receptor control over motivational and cognitive processes. Moreover, the observed increase in [³H]CP55,940 binding in these brain areas likely indicates long-lasting neurobiological adaptations resulting from chronic cocaine self-administration. In conclusion, we demonstrated that chronic cocaine self-administration leads to increased CB1 receptor levels in numerous brain areas and that this neuroadaptation is maintained over a long-lasting extinction period.