Effects of Dehydroepiandrosterone and Alprazolam on Hypothalamic-Pituitary Responses to Exercise

Abstract

The hypothalamic-pituitary-adrenal axis (HPA) is restrained by activation of gamma-amino-butyric acid receptors. Alprazolam (APZ) and dehydroepiandrosterone (DHEA) are purported to be gamma-amino-butyric acid agonists and antagonists, respectively. Our objective was to examine the effects of APZ and DHEA alone and in combination on HPA axis activity. This was a double-blind, crossover, placebo-controlled study. The study setting was the general community. Subjects consisted of 15 men (age, 20-45 yr) with a body mass index of 20-25 kg/m2. DHEA (100 mg/d) or placebo was given for 4 wk, followed by a 2-wk washout; participants ingested 0.5 mg APZ or placebo 10 and 2 h before high-intensity exercise. We measured basal and exercise-induced ACTH, arginine vasopressin (AVP), cortisol, DHEA, and GH responses. It was hypothesized that DHEA would enhance and APZ would blunt exercise-induced ACTH and cortisol release. DHEA significantly increased the AVP response to exercise (P < 0.01). APZ treatment significantly increased basal GH and blunted plasma cortisol, ACTH, AVP, and DHEA responses to exercise (P < 0.05). DHEA and APZ in combination significantly increased the GH response to exercise (P < 0.01). DHEA may alter a subset of receptors involved in AVP release. Together DHEA and APZ may up-regulate GH during exercise by blunting a suppressive (HPA axis) and potentiating an excitatory (glutamate receptor) system.