CHANGES IN RAT SPLEEN CANNABINOID RECEPTORS AFTER CHRONIC CP-55,940 -AN AUTORADIOGRAPHIC STUDY

We examined whether cannabinoid receptor density changes in the rat sp leen after in vivo chronic exposure to cannabinoids. Rats received dai ly injections of 0.4 mg/kg IP of the synthetic cannabinoid receptor li gand CP-55,940 for 11 days. One h after the last injection on day 11, the rats were killed and spleen coronal sections were professed for re ceptor binding autoradiography with 10 nM of [H-3]CP-55,940 in the abs ence or presence of unlabeled CP-55,940 (10 mu M). Densitometric analy sis of the autoradiograms showed significant loss of [H-3]CP-55,940 bi nding of about 42% in chronic cannabinoid-treated, tolerant rats. Our findings indicate that cannabinoid receptors basically present in immu ne spleen cells are down-regulated by chronic exposure to cannabinoids , suggesting a role in immune modulation and in the impairment of immu ne function. (C) 1997 Elsevier Science Inc.