OPIATE PHARMACOLOGY OF MONOAMINE PATHWAYS

这项提案中描述的研究旨在描述 海马区阿片类药物的神经药理学， 伏隔核、内侧前额叶皮质和腹侧 大鼠被盖区(A10区)。我们将使用 电生理和电化学测量技术 对阿片类药物和阿片肽的功能反应。我们的 基本假设是阿片类药物通过多个受体起作用 机制，但任何一个人的细胞机制 受体产生的作用在不同的大脑中是一致的 不同的区域和不同的细胞元素。通过识别 不同受体亚型对阿片类药物作用的影响 区域，并通过确定一个区域内的哪些神经元 鸦片敏感，我们希望能解释“异常”兴奋 可在腹侧被盖区等区域观察到。 此外，我们打算确定在多大程度上预先 突触调节递质释放和突触后 与其他发射器的相互作用有助于总体 阿片肽的作用。 我们将使用电生理技术来表征 这些药物在体外脑片中的直接作用 双眼眼脑移植，人前路异种移植 大鼠眼房和脑干大鼠的原位实验 横断面。我们将用以下方法测量电生理反应 体外脑片和眼球的细胞内记录 移植，体内电化学检测释放 内源性去甲肾上腺素和多巴胺从脑片和 移植，并在细胞外记录自发性和 激起的活动。 在远景目标方面，我们希望将 阿片类药物影响脑电生理的具体途径 可能参与奖赏效应的神经系统 这些毒品。正在确定涉及的受体，以及 它们的激活方式有助于改变 我们希望，含有多巴胺的区域及其靶点的活动 以提供对细胞活动变化的了解 这可能是对滥用药物的行为反应的基础。

The research described in this proposal is intended to characterize the neuropharmacology of opiate drugs in the hippocampus, nucleus accumbens, medial prefrontal cortex, and ventral tegmental area (area A10) of rats. We will use electrophysiological and electrochemical techniques to measure functional responses to opiate drugs and opioid peptides. Our primary hypothesis is that opiates act through multiple receptor mechanisms, but that the cellular mechanism by which any one receptor produces its effects is consistent in different brain regions and on different cellular elements. By identifying the receptor subtypes that mediate opiate effects in different regions, and by determining which neurons within a region are opiate-sensitive, we hope to explain the "anomalous" excitations that are observed in regions such as the ventral tegmental area. In addition, we intend to determine the extent to which pre- synaptic modulation of transmitter release, and postsynaptic interactions with other transmitters contribute to the overall actions of opioid peptides. We will use electrophysiological techniques to characterize the direct actions of these drugs in in vitro brain slices, single and double in oculo brain grafts, in human xenografts to the anterior chamber of the rat eye, and in situ in rats with brain stem transections. We will measure electrophysiological responses with intracellular recording from both in vitro brain slices and in oculo transplants, with in vivo electrochemical detection of the release of endogenous norepinephrine and dopamine from brain slices and transplants, and with extracellular recording of spontaneous and evoked activity. In terms of long-range objectives, we hope to characterize the specific ways in which opiates affect the electrophysiology of neuronal systems that may be involved in the rewarding effects of these drugs. Be determining the receptors that are involved, and the ways in which their activation contributes to changes in activity in dopamine-containing regions and their targets, we hope to provide an understanding of the changes in cellular activity that may underlie behavioral responses to drugs of abuse.