Alprazolam attenuates metabolic stress-induced neuroendocrine and behavioral effects in humans

The effects of benzodiazepine drugs and the role of their recognition site, the GABAA/benzodiazepine receptor, in acute glucoprivic stress are not known. In the present study, the effects of acute glucoprivation were examined in ten healthy human subjects. Glucoprivation was induced by infusion of the glucose analog, 2-deoxyglucose (2DG), at doses sufficient (50 mg/kg) to competitively inhibit glucose metabolism. In addition, the effects of the triazolobenzodiazepine alprazolam (1.5 mg) on the 2DG-induced stress response was assessed. 2DG produced significant elevations in plasma cortisol (P = 0.0001) and glucose (P = 0.0003) levels. Alprazolam pretreatment attenuated the 2DG-related cortisol elevations (P = 0.05) but did not effect 2DG-induced glucose increases. In addition, 2DG caused significant increases in hunger (P = 0.01) and thirst (P = 0.001), and alprazolam significantly blunted both of these responses. Lastly, 2DG had significant effects on heart rate, diastolic blood pressure and body temperature (P less than 0.05). Alprazolam did not effect these physiologic indices. The significance of these data for the mechanisms involved in acute glucoprivic stress are examined and the implications of the data for the pathophysiology of affective illness and eating disorders are discussed.