BRAIN STIMULATION MODELS OF DRUG ABUSE

这是对研究科学家奖(RSA K05)的申请。我的未来 研究将把研究滥用物质作为其主要承诺 以及提供药理学、心理学培训的实验室 以及行为神经科学研究生和博士后。这个 拟议的研究旨在加深我们对 滥用药物奖赏效应的神经元基础 重点关注精神运动兴奋剂和滥用阿片类药物。因为. 先前的研究结果表明，嗅结节可能在 在这两类滥用物质的回报效应中，我们将 我们的一些研究集中在阐明大脑中这一部位。 毒品奖励机制。还将包括补充实验 阿片类药物的止痛作用以及非阿片类药物 药理变量可能与其止痛作用有关。 因为我们发现吗啡诱导的大鼠口腔刻板印象 在注射较低剂量的吗啡几个月后可以重新表达 最初的吗啡治疗我们已经开始了一系列的实验 以确定这些长期影响所涉及的机制。这些 实验可能与阿片类药物滥用以及可能的 内源性阿片系统在多动运动障碍中的作用。 在研究滥用药物的奖赏效应时使用的程序 物质涉及肠外和脑内给药。 受体特异性激动剂和拮抗剂。我们使用的主要方法是 研究这些药物操作的影响是大脑- 刺激性奖赏、药物自我给药与定量2-[14C] 测定局部脑葡萄糖利用率的脱氧葡萄糖法。

This is a request for a Research Scientist Award (RSA K05). My future research will have as its major commitment the study of abused substances as well as provide a laboratory for training of pharmacology, psychology and behavioral neuroscience graduate and postdoctoral students. The proposed research is directed toward furthering our understanding of the neuronal bases of the rewarding effects of abused substances with special emphasis on the psychomotor stimulants and the abused opioids. Because of previous findings suggesting that the olfactory tubercle may play a role in the rewarding effects of these two classes of abused substances we will focus some of our research on the elucidation of this brain site in the mechanism of drug reward. Also included will be complementary experiments of the analgesic effects of opiate drugs and the manner that non- pharmacological variables may contribute to their analgesic effects. Because of our finding that morphine-induced oral stereotypy in the rat can be re-expressed by a comparatively low dose of morphine months after the initial morphine treatment we have embarked on a series of experiments to determine the mechanisms involved in these long term effects. These experiments may have relevance for both opioid abuse as well as a possible role of the endogenous opioid system in hyperkinetic movement disorders. The procedures used in the study of the rewarding effects of abused substances involve the parenteral as well as intracerebral administration of receptor specific agonist and antagonist. The major methods we use to study the effects of these pharmacological manipulations are brain- stimulation reward, drug self-administration and the quantitative 2-[14C) deoxyglucose method of determining local cerebral glucose utilization.