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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system
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Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system

机译：酒精诱导的条件偏好由CB2大麻素受体调节，并改变内皮胆碱系统中的内胆蛋白水平

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摘要

The endocannabinoid (eCB) system is a particularly important neuronal mechanism implicated in alcohol use disorders. Animal models are key to broadening our knowledge of the neurobiological mechanisms underlying alcohol dependence. This study has two main aims: i) to assess how eCB levels in different brain areas are modified by alcohol-induced conditioning place preference (CPP), and ii) to study how cannabinoid type 2 receptor (CB2R) is involved in alcohol-rewarding properties, using pharmacological manipulation in C57BL/6 mice. Our results suggest that the eCB system is dysregulated throughout the mesocorticolimbic system by repeated alcohol exposure during the CPP paradigm, and that levels of anandamide (AEA) and several other N-acylethanolamines are markedly decreased in the medial prefrontal cortex and ventral midbrain of alcohol-CPP mice. We also observed that the administering an antagonist/inverse agonist of the CB2R (AM630) during the acquisition phase of CPP reduced the rewarding effects of alcohol. However, activating CB2R signalling using the agonist JVVH133 seems to reduce both alcohol-and food-rewarding behaviours. Therefore, our findings indicate that the rewarding effects of alcohol are related to its disruptive effect on AEA and other N-acylethanolamine signalling pathways. Thus, pharmacological manipulation of CB2R is an interesting candidate treatment for alcohol use disorders.
机译：Endocannabinoid（ECB）系统是一种特别重要的神经元机制，涉及酒精使用障碍。动物模型是扩大我们对酒精依赖的神经生物学机制知识的关键。本研究有两个主要目的：i），评估不同脑区的ECB水平如何通过酒精诱导的调理地点偏好（CPP）和II）来研究大麻素2受体（CB2R）如何参与酒精奖励性质，在C57BL / 6小鼠中使用药理操作。我们的研究结果表明，在CPP范例期间，通过重复的酒精暴露，在整个中霉素潜水系统中，在整个中央糖尿病的过程中，在内侧预甲状腺皮质和腹侧中脑中，通过重复的酒精暴露，通过重复的酒精暴露，在整个中皮质溶解系统中赘述。在内侧前额叶皮质和腹侧的含量下降CPP小鼠。我们还观察到，在CPP的采集阶段期间施用CB2R（AM630）的拮抗剂/逆激动剂减少了酒精的奖励效果。然而，使用激动剂JVVH133激活CB2R信令似乎减少了酒精和食物奖励行为。因此，我们的研究结果表明，醇的奖励作用与其对AEA和其他N-酰氨乙醇胺信号传导途径的破坏性影响有关。因此，CB2R的药理操纵是醇类使用障碍的有趣候选处理。

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