Department of Psychobiology, Faculty of Psychology, Campus de Somosaguas, Complutense University of Madrid, Madrid, Spain.
Int J Neuropsychopharmacol. 2010 Mar;13(2):191-205. doi: 10.1017/S1461145709991118. Epub 2010 Jan 5.
Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system. Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse. Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis. Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration. WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol. These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.
酒精成瘾的特征是连续的戒断和复发，这是由于中枢神经系统各回路的长期变化所致。越来越多的证据表明，内源性大麻素系统是介导酒精成瘾的最重要的生化系统之一。内源性大麻素系统调节成年神经发生，这是一种发生在大脑几个区域的长期成年可塑性形式，包括齿状回。由于精神药物的暴露会调节成年神经发生，因此神经发生可能与与滥用药物相关的神经生物学疾病的病理生理学有关，因此也可能与治疗有关。在这里，我们研究了成年海马神经发生对酒精和大麻素受体激动剂 WIN 55,212-2（WIN）的敏感性。具体来说，我们分析了酒精复发、大麻素受体激活和成年神经发生之间的潜在联系。成年大鼠暴露于亚慢性酒精 binge 中毒，并接受大麻素受体激动剂 WIN 处理。另一组大鼠接受酒精操作性自我给药任务。这些大鼠中的一半可以持续接触酒精，而另一半则被剥夺酒精，同时或不给予 WIN 处理。WIN 处理在酒精剥夺期间给药时，会导致复发期间酒精摄入量最大增加。强制酒精 binge 中毒和 WIN 处理显著降低了海马神经发生。此外，成年神经发生与酒精的自愿摄入呈负相关。这些发现表明，成年海马神经发生是药物滥用的一个关键因素，它可能为治疗酒精成瘾和依赖提供新的策略。
