BEHAVIORAL AND PHYSIOLOGICAL EFFECTS OF 2-DEOXYGLUCOSE INFUSIONS

2-脱氧葡萄糖(2-DG)是一种葡萄糖类似物，它竞争性地抑制 葡萄糖-6-磷酸脱氢酶并导致细胞内 葡萄糖酸化。在以前的研究中，2-DG已被用作应激源 为了激活下丘脑-垂体-肾上腺(HPA)轴， 交感肾上腺轴和下丘脑的食欲中枢。 我们对这一范例的兴趣来自于临床观察 酗酒者经常摄入更多的碳水化合物 在戒酒之后。为了探索可能的 酒精中毒患者的下丘脑异常 2-DG戒酒，并测量由此产生的行为和 2-DG挑战引起的生理变化。我们假设 2-DG诱导的葡聚糖反应会引起 神经内分泌和行为改变可能阐明 酒精在下丘脑的作用。结果分析显示， 酗酒者在服用2-DG和2-DG后摄入的卡路里比对照组少 安慰剂给药。相反，酗酒者表现出夸张的 下丘脑，促肾上腺皮质激素对葡萄糖代谢的反应。要解决以下问题 这种增强的反应是否是戒酒的急性影响， 这项研究现在正在扩大到包括酗酒者 至少六个月不喝酒。

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.