Cannabinoid Effects on CB1 Receptor Density in the Adolescent Brain: An Autoradiographic Study Using the Synthetic Cannabinoid HU210

The short- and long-term behavioral effects of cannabinoids differ in adolescent and adult rodents. Few studies though have examined the underlying neurochemical changes that occur in the brain following adolescent cannabinoid exposure. In this study, we examined the effect of treatment with the synthetic cannabinoid, HU210, on CB1 receptor density in the brain and on body weight in adolescent male rats. Rats were treated daily with 25, 50, or 100 mu g/kg HU210 for 4 or 14 days, or received a single dose of 100 mu g/kg HU210 and sacrificed 24 h later. Receptor, density was investigated using in vitro autoradiography with the CB1 receptor ligand [H-3] CP55,940. In contrast to adult animals treated under the same paradigm in a previous study, adolescents continued on average, to gain weight over the course of the study. Weight gain was slowest in the 100 mu g/kg group and improved dose dependently with controls gaining the most weight. Following the acute dose of HU210, a trend for a reduction in [H-3] CP55,940 binding and a significant effect of treatment was observed. Statistically significant, dose-dependent, region-specific decreases in binding were observed in all brain regions examined following 4 and 14 days treatment. The pattern of CB1 receptor downregulation was similar to that observed in adults treated with cannabinoids in previous studies; however, its magnitude was smaller in adolescents. This reduced compensatory response may contribute to some acute behavioral effects, the pharmacological cross-tolerance and the long-lasting, adverse psychological consequences of cannabinoid exposure during adolescence. Synapse 64:845-854, 2010. (C) 2010 Wiley-Liss, Inc.