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 both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic adrenal axis and stimulate 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. Preliminary 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.
