Endocannabinoid signaling in hypothalamic-pituitary-adrenocortical axis recovery following stress: effects of indirect agonists and comparison of male and female mice. Pharmacol Biochem Behav 2014 Feb;117:17-24
Date
12/10/2013Pubmed ID
24316201Pubmed Central ID
PMC3929302DOI
10.1016/j.pbb.2013.11.026Scopus ID
2-s2.0-84890264813 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
Studies in male rodents have shown that stress-induced increases in circulating corticosterone are increased by both CB1 receptor (CB1R) antagonist treatment and genetic deletion. The purposes of the current study were to determine whether female mice respond in the same manner as males, and whether indirect CB1R agonists accelerate the return of corticosterone to baseline. In agreement with earlier studies, CB1R null and rimonabant-treated male mice had significantly increased circulating corticosterone 30 min following the end of a restraint episode compared to wild type and vehicle-treated, respectively. Females treated with rimonabant had significantly higher circulating corticosterone compared to vehicle. However, corticosterone concentrations were not different between CB1R null and wild type females at 30 min recovery, although CB1R null mice had higher corticosterone concentrations at 90 min of recovery. Female CB1R null mice exhibited greater serum binding capacity for corticosterone than wild type. The monoacylglycerol lipase inhibitor, JZL184, attenuated corticosterone concentrations at restraint offset in male, and at 30 min recovery in female mice compared to vehicle. Male mice treated with JZL184 exhibited greater concentrations of circulating corticosterone at 120 min recovery, even in the absence of restraint. JZL184 had no effect on corticosterone concentrations in CB1R null mice. The fatty acid amide hydrolase inhibitor, URB597, did not affect corticosterone responses to restraint in male or female, wild type or CB1R null mice. These data suggest that 2-arachidonoylglycerol is the primary endocannabinoid involved in CB1R regulation of the recovery of the HPA axis from restraint stress. These data support a role for endocannabinoid-CB1R signaling in the regulation of the corticosterone response to restraint stress and suggest that female mice with life-long loss of the CB1R undergo compensatory changes that minimize the impact of loss of endocannabinoid signaling on circulating corticosterone.
Author List
Roberts CJ, Stuhr KL, Hutz MJ, Raff H, Hillard CJAuthors
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinHershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin
Christopher J. Roberts MD, PhD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adrenal CortexAnimals
Corticosterone
Endocannabinoids
Female
Hypothalamo-Hypophyseal System
Male
Mice
Mice, Inbred ICR
Mice, Knockout
Piperidines
Pituitary-Adrenal System
Pyrazoles
Receptor, Cannabinoid, CB1
Signal Transduction
Stress, Physiological
