OPIATE AND COCAINE INTERACTIONS WITH REWARD PATHWAYS

本提案中描述的研究旨在调查 阿片类药物和可卡因的中枢作用机制(S) 啮齿动物系统。我们将使用电生理技术来 描述这些药物在不同环境中的直接和间接作用 眼脑单层和双层体外脑片的脑区 移植物，在急性麻醉的制剂中原位，并在 未麻醉的长期植入的动物。我们将衡量 细胞内记录技术的电生理反应，以及 用细胞外记录自发单位活动和诱发场 回应。我们的主要假设是动物会自我管理这些 因为药物管理的某些强化方面，而且 这种强化依赖于中央的单胺能底物。 神经系统。因此，我们将尝试确定鸦片类药物是否 像吗啡和可卡因这样的药物似乎有共同的 单胺类“奖赏”系统的电生理作用 这可能为其共同的神经药理作用提供依据。 在长远目标方面，我们希望明确以下机制： 阿片剂和可卡因在强化相关系统中的作用 它们在其他神经系统中的作用(例如，参与 止痛等)。如果我们能确定这些药物有共同的 在特定大脑区域的作用机制，或与 特定的神经递质，那么我们就有了预测 基于某种药理学标准的药物滥用潜力。 最终，这可能会使我们更好地理解 药物滥用的一般情况，特别是哪种生物基础 这可能是滥用药物使用的个体差异的基础。

The research described in this proposal is intended to investigate the mechanism(s) of action of opiate drugs and cocaine in the central nervous systems of rodents. We will use electrophysiological techniques to characterize the direct and indirect actions of these drugs in various brain regions in in vitro brain slices, single and double in oculo brain grafts, in situ in acutely anaesthetized preparations, and in unanaesthetized chronically implanted animals. We will measure electrophysiological responses with intracellular recording techniques, and with extracellular recording of spontaneous unit activity and evoked field responses. Our primary hypothesis is that animals self-administer these drugs because of some reinforcing aspect of drug administration, and that such reinforcement depends upon a monoaminergic substrate in the central nervous system. Therefore, we will attempt to determine whether opiate drugs such as morphine and cocaine appear to have a common electrophysiological action on this putative monoamine "reward" system which might provide a basis for their common neuropharmacological actions. In terms of long-range objectives, we hope to define the mechanisms of action of opiates and cocaine in reinforcement-related systems, as opposed to their actions in other neuronal systems (e.g., those involved in analgesia, etc.). If we can establish that these drugs have a common mechanism of action in a particular brain region, or in relation to a specific neurotransmitter, then we would have a basis for predicting the abuse potential of drugs based upon some pharmacological criterion. Ultimately, this might lead to a better understanding of the phenomenon of drug abuse in general, and in particular what kinds of biological bases which might underlie individual differences in the use of abused drugs.