Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic–pituitary–adrenal axis and other consequences of daily repeated stress

摘要: Abstract There is evidence that endogenous cannabinoids (eCBs) play a role in the control of hypothalamic–pituitary–adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data rats suggest eCBs, acting through CB1 receptors (CB1R), may be involved adaptation HPA axis daily repeated stress. In present study we analyze this issue male mice rats. Using knock-out for receptor (CB1−/−) showed mutant presented similar adrenocorticotropic hormone (ACTH) response first IMO as wild-type mice. Daily exposure 1 h immobilization reduced ACTH stressor, regardless genotype, demonstrating occurred same extent absence CB1R. Prototypical changes observed after stress such enhanced corticotropin releasing factor (CRH) gene expression paraventricular nucleus hypothalamus, impaired body weight gain thymus were similarly both genotypes. The lack effect CB1R another stressor (restraint) was confirmed CD1 by antagonist AM251 just before last Finally, latter drug did not blunt HPA, glucose behavioral forced swim Thus, results indicate critical overall effects or proper