NEUROBIOLOGY OF OPIOID-DOPAMINE INTERACTIONS

滥用药物会产生强烈的积极强化作用， 部分由腹侧被盖区(VTA)调节 多巴胺(DA)能神经元。例如，老鼠会自我管理。 海洛因或吗啡直接进入VTA并系统性地 使用阿片类或多巴胺拮抗剂将减轻这种影响 行为。微离子电泳法将吗啡直接应用于 VTA DA神经元产生的兴奋被阿片类药物阻断 拮抗剂纳洛酮。因为这些神经元是一个重要的部分 大脑的内源性奖赏系统，激活它们的药物 (如鸦片类药物、兴奋剂、酒精和尼古丁) 滥用的可能性。目前的赠款将利用以下几点 用于表征结构属性的技术 调节VTA DA神经元输出的内源性阿片系统 大鼠：(1)光镜免疫组织化学染色 将使用技术来确定轴突的位置 三种阿片肽神经元的终末 (脑啡肽、β-内啡肽和强啡肽)在三维 VTA间隙；(2)电子显微镜免疫组织化学 染色技术将被用来确定阿片类药物 突触接触与大脑中的DA和/或非DA神经元有关。 VTA；(3)逆行神经解剖示踪与原位 杂交技术将一起用于确定 神经支配的含阿片肽的胞体定位 VTA；以及(4)定量受体放射自显影技术 将被用来确定阿片受体的位置 3维空间内的亚型(Mu三角洲，kappa) VTA以及它们的数量和亲和力。澄清： 阿片类和VTA DA神经元之间的结构关系将 提供了了解神经元的重要一步 构成大脑内源性奖励机制的回路/S， 为合理治疗药物滥用提供了依据 接近了。

Drugs of abuse produce strong positive reinforcing effects which are mediated, in part, by the ventral tegmental area (VTA) dopaminergic (DA) neurons. Rats, for example, will self-administer heroin or morphine directly into the VTA and systemically administered opioid- or DA-antagonists will attenuate this behavior. Microiontophoretic application of morphine directly onto VTA DA neurons produces excitation which is blocked by the opioid antagonist naloxone. Because these neurons are an important part of the brain's endogenous reward system, drugs which activate them (such as opiates, stimulants, alcohol, and nicotine) possess a high abuse potential. The present grant will utilize the following techniques to characterize the structural properties of the endogenous opioid systems which regulate VTA DA neuronal output in the rat: (1) light microscopic immunohistochemical staining techniques will be used to determine the location of the axon terminals of the three opioid peptide-containing neurons (enkephalin, beta-endorphin and dynorphin) within the 3-dimensional space of the VTA; (2) electron microscopic immunohistochemical staining techniques will be used to determine whether the opioid synaptic contacts are made with DA and/or non-DA neurons within the VTA; (3) retrograde neuroanatomical tracing and in situ hybridization techniques will be used together to determine the location of the opioid peptide-containing somata which innervate the VTA; and (4) quantitative receptor autoradiography techniques will be used to determine the location of the opioid receptor subtypes (mu delta, kappa) within the 3-dimensional space of the VTA, and their numbers and affinities. Elucidation of the structural relationships between the opioid and VTA DA neurons will provide an important step toward understanding the neuronal circuits which make up the brain's endogenous reward mechanism/s, and provide a foundation for rational drug abuse treatment approaches.