Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus

Matthew N. Hill, Erica J. Carrier, W. S.Vanessa Ho, Leyu Shi, Sachin Patel, Boris B. Gorzalka, Cecilia J. Hillard

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


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 CB1 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 CB1 receptor without affecting affinity for the CB1 receptor agonist, [3H]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 CB1 receptor is under negative regulation by glucocorticoids in the hippocampus, and suggest that hippocampal cannabinoid CB1 receptor signaling could be reduced under conditions associated with hypersecretion of glucocorticoids, such as chronic Stress.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
Issue number2
StatePublished - 2008
Externally publishedYes


  • 2-arachidonylglycerol
  • Anandamide
  • Corticosterone
  • Depression
  • Endocannabinoid

ASJC Scopus subject areas

  • Cognitive Neuroscience


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