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 processed for receptor binding autoradiography with 10 nM of [3H]CP-55,940 in the absence or presence of unlabeled CP-55,940 (10 microM). Densitometric analysis of the autoradiograms showed significant loss of [3H]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.
Massi
P
P
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Patrini
G
G
Rubino
T
T
Fuzio
D
D
Parolaro
D
D
D000818:Animals; D001345:Autoradiography; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
D002186:Cannabinoids; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol