OPIATE AND COCAINE INTERACTIONS WITH REWARD PATHWAYS

本提案中所述的研究旨在调查 阿片类药物和可卡因在中枢神经系统中的作用机制 啮齿动物系统。 我们将使用电生理技术 描述这些药物在各种情况下的直接和间接作用 体外脑切片中的脑区域，单眼脑和双眼脑 移植物，在急性麻醉制剂中原位， 未麻醉的长期植入动物。 我们将测量 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 应答 我们的主要假设是动物自我管理这些 因为药物管理的一些强化方面， 这种增强依赖于中心的单胺能底物， 神经系统 因此，我们将尝试确定鸦片是否 吗啡和可卡因等药物似乎有一个共同的 电生理作用在这个假定的单胺“奖励”系统 这可能为它们共同的神经药理学作用提供了依据。 就长期目标而言，我们希望确定 鸦片剂和可卡因在麻醉品相关系统中的作用， 它们在其他神经元系统中的作用（例如，那些参与 镇痛等）。 如果我们能确定这些药物 在特定的大脑区域的作用机制，或与一个 特定的神经递质，那么我们将有一个基础来预测 根据某些药理学标准确定药物滥用的可能性。 最终，这可能会导致更好地理解 药物滥用，特别是什么样的生物基础， 这可能是滥用药物的个体差异的基础。

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.