Changes in rat spleen cannabinoid receptors after chronic CP-55,940: An autoradiographic study

We examined whether cannabinoid receptor density changes in the rat spleen after in vivo chronic exposure to cannabinoids. Rats received daily injections of 0.4 mg/kg IP of the synthetic cannabinoid receptor ligand 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 receptor binding autoradiography with 10 nM of [H-3]CP-55,940 in the absence or presence of unlabeled CP-55,940 (10 mu M). Densitometric analysis of the autoradiograms showed significant loss of [H-3]CP-55,940 binding of about 42% in chronic cannabinoid-treated, tolerant rats. Our findings indicate that cannabinoid receptors basically present in immune spleen cells are down-regulated by chronic exposure to cannabinoids, suggesting a role in immune modulation and in the impairment of immune function. (C) 1997 Elsevier Science Inc.