Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration
Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration
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DOI：
10.1523/jneurosci.4403-06.2007
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发表时间：
2007-04-04
影响因子：
5.3
通讯作者：
Parsons, Loren H.
中科院分区：
文献类型：
--
作者：
Caille, Stephanie;Alvarez-Jaimes, Lily;Parsons, Loren H.
乙醇和阿片类药物自我管理是敏感的大麻素CB（1）受体功能的操纵，并从这一点，内源性大麻素系统在药物奖励的调制作用已被假设。然而，直接的体内证据表明，药物诱导的脑内源性大麻素（eCB）形成的变化一直缺乏。为了解决这个问题，我们探讨了药物自我管理的影响，间质eCB水平的核延髓（NAc）壳使用体内微透析。乙醇，海洛因和可卡因进行了比较，因为乙醇和海洛因的奖励性能降低CB 1受体失活，而可卡因奖励是不太敏感，这些操作。乙醇自我给药显著增加了透析液2-花生四烯酰甘油（2-AG）水平，而透析液花生四烯酰胺（AEA）浓度没有伴随变化。相反，海洛因自我管理显着增加透析液AEA水平，并诱导一个微妙的，但显着降低透析液2-AG水平。在每种情况下，透析液eCB含量的相对变化与消耗的药物量显著相关。相比之下，可卡因自我管理并没有改变透析液水平的AEA或2-AG。CB 1拮抗剂SR 141716 A局部输注到NAc显着减少乙醇，但不是可卡因，自我管理。结合我们先前观察到的NAc内SR 141716 A减少海洛因自我给药，这些数据为eCB参与乙醇和海洛因而不是可卡因的动机特性提供了新的体内支持。此外，乙醇和海洛因对间质2-AG和AEA的选择性作用为这两种滥用物质产生的不同神经化学特征提供了新的见解。
Ethanol and opiate self-administration are sensitive to manipulations of cannabinoid CB(1) receptor function and, from this, a role for the endogenous cannabinoid system in the modulation of drug reward has been hypothesized. However, direct in vivo evidence of drug-induced alterations in brain endocannabinoid (eCB) formation has been lacking. To address this issue, we explored the effect of drug self-administration on interstitial eCB levels in the nucleus accumbens (NAc) shell using in vivo microdialysis. Ethanol, heroin, and cocaine were compared because the rewarding properties of ethanol and heroin are reduced by CB1 receptor inactivation, whereas cocaine reward is less sensitive to these manipulations. Ethanol self-administration significantly increased dialysate 2-arachidonoylglycerol (2-AG) levels with no concomitant change in dialysate anandamide ( AEA) concentrations. Conversely, heroin self-administration significantly increased dialysate AEA levels, and induced a subtle but significant decrease in dialysate 2-AG levels. In each case, the relative change in dialysate eCB content was significantly correlated with the amount of drug consumed. In contrast, cocaine self-administration did not alter dialysate levels of either AEA or 2-AG. Local infusion of the CB1 antagonist SR 141716A into the NAc significantly reduced ethanol, but not cocaine, self-administration. Together with our previous observation that intra-NAc SR 141716A reduces heroin self-administration, these data provide novel in vivo support for an eCB involvement in the motivational properties of ethanol and heroin but not cocaine. Furthermore, the selective effects of ethanol and heroin on interstitial 2-AG and AEA provide new insight into the distinct neurochemical profiles produced by these two abused substances.