Roles for the endocannabinoid system in ethanol-motivated behavior

摘要: Alcohol use disorder represents a significant human health problem that leads to substantial loss of life and financial cost society. Currently available treatment options do not adequately address this problem, thus, additional therapies are desperately needed. The endocannabinoid system has been shown, using animal models, modulate ethanol-motivated behavior, it also demonstrated chronic ethanol exposure can have potentially long-lasting effects on the system. For example, ethanol, in either cell culture or preclinical rodent causes an increase levels results down-regulation cannabinoid receptor 1 (CB1) uncoupling from downstream G protein signaling pathways. Using positron emission tomography (PET), similar CB1 noted multiple regions brain alcoholic patients. In rodents, with inverse agonist SR141716A (Rimonabant), genetic deletion reduction voluntary drinking, ethanol-stimulated dopamine release nucleus accumbens, operant self-administration sensitization locomotor reinstatement/relapse behavior. Although clinical utility Rimonabant other antagonists/inverse agonists for is limited due negative neuropsychiatric side effects, allosteric modulators inhibitors catabolism represent therapeutic targets worthy examination.