2-deoxyglucose (2-DG) is a glucose analog which competitively inhibits glucose-6-phosphate dehydrogenase and leads to intracellular glucoprivation. In previous studies, 2-DG has been used as a stressor to activate the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic adrenal axis and the appetitive centers of the hypothalamus. Our interest in this paradigm was generated by the clinical observation that alcoholics frequently consume increased amounts of carbohydrates following cessation of drinking. In order to explore possible hypothalamic abnormalities in patients with alcoholism, we administered 2-DG to abstinent alcoholics and measured the resulting behavioral and physiological changes arising from the 2-DG challenge. We postulated that a 2-DG induced glucoprivic response would give rise to both neuroendocrine and behavioral changes that might elucidate mechanisms of alcohol's action in the hypothalamus. Analysis of the results show alcoholics consume less calories than controls following both 2-DG and placebo administration. Conversely, alcoholics show an exaggerated hypothalamic, ACTH response to glucoprivation. To address the issue of whether this increased response is an acute effect of alcohol withdrawal, the study is now being expanded to include alcoholics who have been alcohol-free for at least six months.
