Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice.

摘要: Hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity is associated with major depressive disorders, and treatment classical antidepressants ameliorates not only psychopathological symptoms, but also the dysregulation of HPA axis. Here, we further elucidated role impaired cannabinoid type 1 receptor (CB1) signaling for neuroendocrine behavioral stress coping in mouse forced swim test (FST). We demonstrate that genetic inactivation CB1 accompanied by increased plasma corticosterone levels both under basal conditions at different time points following exposure to FST. The latter effect could be mimicked C57BL/6N mice acute, subchronic, chronic administration selective antagonist SR141716. Further experiments confirmed specificity corticosterone-elevating SR141716 actions CB1-deficient mice. Subchronic pharmacological blockade CB1, its deletion, induced antidepressant-like responses FST were characterized decreased floating and/or struggling behavior. effects acute desipramine absent mice, dampening on stress-induced secretion compromised deficiency. However, intact pre-treated SR141716, indicating potential developmental deficits conclude shares desipramine, reveals opposite activity.