Involvement of neurosteroid mechanism in the adrenocorticotrophin-induced behavioral effects in rats

Although adrenocorticotrophin (ACTH) produces a variety of neurobehavioral effects, the mechanisms by which ACTH exerts these behavioral effects are unknown. In the present study, the possible involvement of neurosteroids in the behavioral and neuroendocrine actions following systemic administration of ACTH was examined in rats. ACTH (50-200 mU/ kg, s.c.) dose-dependently decreased behavioral activity in the actimeter and produced significant anxiolytic and anti-risk activity in the plus-maze behavior test, without influencing antinociception, thermoregulation and systolic blood pressure. ACTH also increased the plasma corticosterone and depleted adrenal ascorbic acid level in a dose-dependent manner. Pretreatment with metyrapone (20 and 50 mg/kg, i.p.), an inhibitor of steroid 11-hydroxylase and endogenous steroidogenesis, significantly blocked the ACTH (100 mU/kg)-induced behavioral and neuroendocrine effects. A combined exposure of ACTH and allopregnanolone (0.5 mg/kg, s.c.), a GABA-A active neurosteroid, significantly potentiated the behavioral responsiveness to ACTH without affecting the adrenal responsiveness. The potentiating effects of allopregnanolone when administered simultaneously with ACTH could be due to the endogenous pooling of pregnane neurosteroids with synergistic properties following ACTH administration These results indicate a role for neurosteroid mechanisms in the behavioral effects of ACTH.

Involvement of neurosteroid mechanism in the adrenocorticotrophin-induced behavioral effects in rats Academic Article