Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus.
Experimental studies indicate a bidirectional, functional relationship between glucocorticoids and the endocannabinoid system; however, the effects of repeated glucocorticoid treatment on the endocannabinoid system have not been examined. In this study, we treated male rats with either a single dose or a 21-day course of treatment with corticosterone (20 mg/kg) and measured hippocampal cannabinoid CB(1) receptor expression and endocannabinoid content. The 21-day, but not the single, administration of corticosterone significantly reduced both the binding site density and amount of protein of the hippocampal cannabinoid CB(1) receptor without affecting affinity for the CB(1) receptor agonist, [(3)H]CP55940. With regard to hippocampal endocannabinoid content, acute corticosterone treatment resulted in a significant reduction in anandamide but did not affect 2-arachidonylglycerol, while repeated corticosterone treatment did not alter content of either anandamide or 2-arachidonylglycerol. These data support the hypothesis that the cannabinoid CB(1) receptor is under negative regulation by glucocorticoids in the hippocampus, and suggest that hippocampal cannabinoid CB(1) receptor signaling could be reduced under conditions associated with hypersecretion of glucocorticoids, such as chronic stress.
Hill
Matthew N
MN
Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
Carrier
Erica J
EJ
Ho
W-S Vanessa
WS
Shi
Leyu
L
Patel
Sachin
S
Gorzalka
Boris B
BB
Hillard
Cecilia J
CJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D014316:Tritium
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D003511:Cyclohexanols; D063388:Endocannabinoids; D005989:Glycerides; D007166:Immunosuppressive Agents; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D014316:Tritium; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C094503:glyceryl 2-arachidonate; C078814:anandamide; D003345:Corticosterone