GENDER DIFFERENCE IN COCAINE-INDUCED HPA AXIS ACTIVATION

The study investigates the influence of gender on the activation of th e hypothalamo-pituitary-adrenal (HPA) axis by cocaine and other monami ne uptake inhibitors. Drug-induced secretion of adrenocorticotrophic h ormone (ACTH) was used to pursue this question. Cocaine produced a dos e-related rise in serum ACTH levels in both male and female rats, but the rise was significantly greater in females than in males. Females a lso showed enhanced HPA axis activation following administration of th e dopamine uptake inhibitor GBR 12909, the serotonin uptake inhibitor fluoxetine, and the norepinephrine uptake inhibitor desipramine. No ge nder difference in HPA axis activation was observed in a dose-response study of cocaine-induced HPA activation in 10 day old rats. Ovariecto my of females decreased the ACTH response to cocaine, but castration d id not affect the response of males. To evaluate the role of the pitui tary in this gender difference, ACTH levels were determined after cort icotropin-releasing factor (CRF) administration. Females showed greate r ACTH responses to CRF than males. These studies demonstrate that fem ale rats show exaggerated HPA responses to monoamine uptake inhibitors and that enhanced pituitary responsivity to CRF contributes to this g ender difference. (C) 1997 American College of Neuropsychopharmacology .