期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：3
页码：1393-1398
DOI：10.1073/pnas.0336351100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cannabinoids and ethanol can activate the same reward pathways, which could suggest endocannabinoid involvement in the rewarding effects of ethanol. The high ethanol preference of young (6-10 weeks) C57BL/6J mice is reduced by the cannabinoid receptor 1 (CB1) antagonist SR141716A to levels observed in their CB1 knockout littermates or in old (26-48 weeks) wild-type mice, in both of which ethanol preference is unaffected by SR141716A. Similarly, SR141716A inhibits food intake in food-restricted young, but not old, wild-type mice. There are no age-dependent differences in the tissue levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or the density of CB1 in the hypothalamus, limbic forebrain, amygdala, and cerebellum. CB1-stimulated guanosine 5'-[{gamma}-thio]triphosphate (GTP[{gamma}S]) binding is selectively reduced in the limbic forebrain of old compared with young wild-type mice. There is no age-dependent difference in Gi or Go subunit protein expression in the limbic forebrain, and the selective reduction in GTP[{gamma}S] labeling in tissue from old mice is maintained in a receptor/G protein reconstitution assay by using functional bovine brain G protein. These findings suggest that endocannabinoids acting at CB1 contribute to ethanol preference, and decreased coupling of CB1 to G proteins in the limbic forebrain by mechanisms other than altered receptor or G protein levels may be involved in the age-dependent decline in the appetite for both ethanol and food.
