Details

Autor(en) / Beteiligte

• Roberts, Christopher J.
• Stuhr, Kara L.
• Hutz, Michael J.
• Raff, Hershel
• Hillard, Cecilia J.

Titel

Endocannabinoid signaling in hypothalamic–pituitary–adrenocortical axis recovery following stress: Effects of indirect agonists and comparison of male and female mice

Ist Teil von

• Pharmacology, biochemistry and behavior, 2014-02, Vol.117, p.17-24

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 30min 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 30min recovery, although CB1R null mice had higher corticosterone concentrations at 90min 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 30min recovery in female mice compared to vehicle. Male mice treated with JZL184 exhibited greater concentrations of circulating corticosterone at 120min 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. •CB1 receptor antagonism results in elevated circulating corticosterone after stress.•Male not female CB1 receptor null mice exhibit greater corticosterone after stress.•Monoacylglycerol lipase inhibition reduces corticosterone immediately after stress.•Corticosterone is increased 3 hours after monoacylglycerol lipase inhibition.•The role of CB1 receptor in the regulation of corticosterone release is complex.