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Monday, March 26, 2007

Bidirectional Alterations of Hippocampal Cannabinoid 1 Receptors and Their Endogenous Ligands in a Rat Model of Alcohol Withdrawal and Dependence

The hippocampus is strongly implicated in memory processes and contains high concentrations of both cannabinoid receptors and their endogenous ligands. Chronic alcohol consumption impairs a variety of cognitive and performance tasks, including memory and learning. As the activation of cannabinoid receptors by their endogenous ligands modulates hippocampal neurotransmission, we hypothesized that the impaired memory and learning in alcoholism may be due to alterations in the hippocampal endocannabinoid system.

These data demonstrate that CIE treatment and withdrawal transiently down-regulates hippocampal CB1Rs followed by a long-term up-regulation, including increased levels of endogenous cannabinoids.

These findings are consistent with our hypothesis and suggest that long-term up-regulation of hippocampal CB1Rs may contribute to the long-term cognitive impairments in alcoholism.

The data further suggest that the effectiveness of CB1R blockade in decreasing alcohol consumption may be greater after protracted abstinence from alcohol.



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