Innate difference in the endocannabinoid signaling and its modulation by alcohol consumption in alcohol-preferring sP rats

The present study examined whether genetically predetermined differences in the components of the endocannabinoid system exist in the brain of Sardinian alcohol-preferring (sP) and Sardinian alcohol-non preferring (sNP) rats, a pair of rat lines selectively bred for opposite alcohol preference. The effects of acquisition and maintenance of alcohol drinking, alcohol withdrawal, and alcohol re-exposure on the endocannabinoid system were also investigated in the striatum of sP rats. The findings revealed significantly higher levels of the CB1 receptors, CB1 receptor mRNA, CB1 receptor-mediated G-protein coupling and endocannabinoids in the cerebral cortex, hippocampus and striatum of alcohol-naive sP rats than sNP rats. A significantly lower expression of mFAAH enzyme was evident in the hippocampus of alcohol-naive sP rats. Alcohol drinking (during both acquisition and maintenance phases) in sP rats resulted in a significant reduction in the striatal CB1 receptor-mediated G-protein coupling whereas alcohol withdrawal attenuated this effect. Alcohol consumption was also associated with marked elevation in the endocannabinoids in the striatum. Co-administration of the CB1 receptor antagonist, rimonabant (SR141716A), reduced alcohol drinking, and reversed alcohol-induced changes in the CB1 receptor-mediated G-protein coupling. These findings provided a new insight into a genetic basis of excessive alcohol consumption, suggesting innate differences in the endocannabinoid system may be associated with higher alcohol preference in sP rats. The data also indicate modulation of the CB1 receptor-mediated signaling by alcohol consumption and further strengthen the hypothesis that the endocannabinoid system could be a target for the treatment of alcohol related behaviors.