Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis

Abstract

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.