BRAIN STIMULATION MODELS OF DRUG ABUSE

描述：(申请人摘要) 拟议的研究致力于进一步了解 对滥用鸦片类药物和可卡因的依赖的神经元基础。 以前的研究已经表明，有延长效应的几周 在最后几次高剂量的吗啡之后，因此焦点将是 关于可卡因和阿片类药物对这些变化的解释 用定量2-脱氧-D-[L-14C]葡萄糖(2-DG)测定 脑部局部代谢利用葡萄糖的测定。 因为这些效应被条件性药物提示增强了 拟议的实验将详细探讨这些因素的影响 对延长效果的条件性暗示。此外，实验， 将进行的是确定兴奋性氨基酸的作用 关于这些药物滞留效应的表现以及作用 γ-氨基丁酸、腺苷、多巴胺-DL受体和环磷酸腺苷系统 调节可卡因和海洛因的奖励效应和摄入量。 这些实验加在一起，将允许进一步 对大脑奖励系统在调节两者中的作用的理解 滥用物质的急性和长期影响。这些是旷日持久的 在停止用药后很久才出现的影响，有很大的 这对于理解渴求现象具有重要意义。使用 这一知识可以合理地开发出有效的治疗方法。 除了2-DG程序外，实验还将使用药物自身 给药、脑刺激奖励和条件性场所 偏好，所有用来研究虐待的奖励效应的模型 物质。实验动物将成为老鼠。

DESCRIPTION: (Applicant's Abstract) The proposed research is committed to the further understanding of the neuronal bases of dependence to the abused opiates and cocaine. Previous work has indicated that there are protracted effects weeks after the last of a few high doses of morphine, therefore focus will be on the elucidation of these changes with cocaine as well as opiates using the quantitative 2-deoxy-D-[l-14C]glucose (2-DG) for the determination of local cerebral metabolic utilization of glucose. Because these effects were enhanced by conditioned drug cues the proposed experiments will explore in detail the effects of these conditioned cues on the protracted effects. In addition, experiments will be carried out to determine the role of the excitatory amino acids on the expression of these protracted drug effects as well as the role of GABA, adenosine, dopamine Dl receptor, and cyclic AMP systems in modulating the rewarding effects and intake of both cocaine and heroin. The experiments, taken together, will allow for the further understanding of the role of the brain reward system in mediating both the acute and protracted effects of abused substances. These protracted effects, present long after cessation of drug administration, have major importance for the understanding of the phenomenon of craving. With this knowledge effective therapies may be rationally developed. In addition to the 2-DG procedure the experiments will employ drug self- administration, brain-stimulation reward, and conditioned place preference, all models used to study the rewarding effects of abused substances. The experimental animal will be the rat.