BRAIN STIMULATION MODELS OF DRUG ABUSE

描述：（申请人摘要） 本研究旨在进一步了解 依赖滥用阿片类药物和可卡因的神经基础。 以前的工作表明，有持久的影响周 在最后几次大剂量的吗啡后，因此，重点将是 对可卡因和鸦片制剂的这些变化的解释 使用定量2-脱氧-D-[1 - 14 C]葡萄糖（2-DG） 局部脑葡萄糖代谢利用的测定。 因为这些效应被条件性药物刺激所增强， 拟议的实验将详细探讨这些影响， 条件线索的持久效应。 此外，实验 将进行，以确定兴奋性氨基酸的作用 对这些持久的药物作用的表达以及 GABA、腺苷、多巴胺D1受体和环AMP系统在 调节可卡因和海洛因的奖赏效应和摄入量。 这些实验结合在一起，将允许进一步的 了解大脑奖励系统在调解两者中的作用 滥用药物的急性和长期影响。 这些旷日持久的 在停止给药后很长时间内存在的影响， 对理解渴望现象的重要性。 与 这种知识可以合理地开发有效的治疗方法。 除了2-DG程序外，实验还将采用药物自我- 管理、脑刺激奖励和条件化场所 偏好，所有用于研究虐待的奖励效应的模型 物质. 实验动物为大鼠。

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.