Abstinent alcoholics exhibit an exaggerated stress response to 2-deoxy-D-glucose challenge

Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism; however, the mechanism and clinical significance of this disturbance are poorly understood. We used 2-deoxy-D-glucose (2-DG), which produces intracellular glucoprivation, to compare neurochemical, physiological, and behavioral responses to glucoprivic stress between alcoholics abstinent for 3 weeks and healthy volunteers. Twenty-six male alcoholics and 15 male healthy volunteers received intravenous infusions of placebo, 12.5 mg/kg, and 25.0 mg/kg of body weight of 2-DG over 30 min on three separate days, following a random-ordered, double-blind procedure. Minimal effects were observed following administration of the 12.5 mg/kg of body weight dose of 2-DG. Following 25.0 mg/kg, alcoholics showed both exaggerated ACTH and cortisol responses and greater increases in caloric intake when compared with controls. Although anxiety, desire to consume alcohol, plasma progesterone, and sympathetic and adrenal medullary activity all increased following 2-DG, these responses did not differ between alcoholics and controls. The present findings suggest certain specificity for the exaggerated hypothalamic and adrenocortical responses to mild glucoprivic stress in 3-week-abstinent alcoholics.