Genetic and pharmacological manipulations of the CB1 receptor alter ethanol preference and dependence in ethanol preferring and nonpreferring miceSynapse 62:574-581, 2008
Recent studies have indicated a role for the endocannabinoid system in ethanol-related behaviors.
This study examined the effect of pharmacological activation, blockade, and genetic deletion of the CB1 receptors on ethanol-drinking behavior in ethanol preferring C57BL/6J (B6) and ethanol nonpreferring DBA/2J (D2) mice.
The deletion of CB1 receptor significantly reduced the ethanol preference. Although the stimulation of the CB1 receptor by CP-55,940 markedly increased the ethanol preference, this effect was found to be greater in B6 than in D2 mice. The antagonism of CB1 receptor function by SR141716A led to a significant reduction in voluntary ethanol preference in B6 than D2 mice.
A significant lower hypothermic and greater sedative response to acute ethanol administration was observed in both the strains of CB1 -/- mice than wild-type mice. Interestingly, genetic deletion and pharmacological blockade of the CB1 receptor produced a marked reduction in severity of handling-induced convulsion in both the strains.
The radioligand binding studies revealed significantly higher levels of CB1 receptor-stimulated G-protein activation in the striatum of B6 compared to D2 mice. Innate differences in the CB1 receptor function might be one of the contributing factors for higher ethanol drinking behavior.
The antagonists of the CB1 receptor may have therapeutic potential in the treatment of ethanol dependence.
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