OPIOID EFFECTS ON NUCLEUS BASALIS CHOLINERGIC NEURONS

本申请的长期目标是更好地了解 麻醉品滥用的生物学基础。 吗啡是一种有效的麻醉剂， 药物与大脑阿片受体相互作用的表现。 的 腹侧苍白球/基底核（VP/nB）富含阿片结合位点。 VP/nB的主要神经元群是含乙酰胆碱的神经元群。 这些细胞对刺激表现出条件相关的反应 之前的加固。 脑啡肽能末梢进行突触接触 VP/nB胆碱能神经元;然而， 这种相互作用在很大程度上是未知的。 假设：脑啡肽能输入 VP/nB胆碱能神经元介导的方面的加强。 提出 具体目标： I. 描述脑啡肽能神经递质的药理学和生理学特征 预测VP/NB。 假定的胆碱能神经元将 体内电生理学特征和突触药理学 将使用微离子电渗疗法应用评估阿片受体 受体特异性阿片激动剂和拮抗剂。 半胆属 结合（指示胆碱能活性）将用于 评估VP/nB内微量注射 阿片类药物。 二. 研究VP/nB神经元和阿片受体在大鼠海马神经元的参与， 滥用毒品的可能性。 受体的强化特性- 将评估微注射到VP/nB中的特异性阿片激动剂 使用条件位置偏好范例。 电生理记录 将检查从VP/nB记录的单个单位活动 当动物处于先前与吗啡配对的环境中时 (CS+），或与媒介物配对（CS-）。 还将比较 神经元放电和动物的自发行为。 以确定是否 公差发展到上述参数，将进行实验 在长期使用吗啡的大鼠中。 VP/nB胆碱能神经元参与强化，然而，这些神经元参与强化。 细胞尚未进行神经生物学研究， 阿片类药物滥用的潜在机制。 在拟议中取得的成果 实验应该传授必要的信息，神经生物学的， VP/nB，还提供了重要的信息，有助于设计 治疗麻醉品滥用的适当药理学策略。

The LONG TERM OBJECTIVE of this application is to better understand the biological basis of narcotic abuse. Morphine is a potent reinforcer, a manifestation of the drug interacting with brain opioid receptors. The ventral pallidum/nucleus basalis (VP/nB) is rich with opioid binding sites. A major neuronal population of the VP/nB is the acetylcholine-containing cells and these cells exhibit conditioning-related responses to stimuli preceding reinforcement. Enkephalinergic terminals make synaptic contact with VP/nB cholinergic neurons; however, the functional consequences of this interaction is largely unknown. HYPOTHESIS: Enkephalinergic inputs to VP/nB cholinergic neurons mediate aspects of reinforcement. Proposed SPECIFIC AIMS: I. To characterize the pharmacology and physiology of enkephalinergic projections to the VP/nB. Putative cholinergic neurons will be electrophysiologically characterized in vivo, and the synaptic pharmacology of opioid receptors will be evaluated using microiontophoretic application of receptor-specific opioid agonists and antagonists. Hemicholinium binding, which is indicative of cholinergic activity, will be used to assess cholinergic terminal function after intra-VP/nB microinjection of the opioid agents. II. To study the involvement of VP/nB neurons and opioid receptors in the abuse potential of narcotics. The reinforcing properties of receptor- specific opioid agonists microinjected into the VP/nB will be assessed using a condition place preference paradigm. Electrophysiologic recordings in behaving rats will examine single-unit activity recorded from the VP/nB while the animal is in an environment previously paired with morphine (CS+), or paired with vehicle (CS-). Comparisons also will be made between neuronal firing and the animals' spontaneous behavior. To determine if tolerance develops to the above parameters, experiments will be conducted in rats chronically treated with morphine. VP/nB cholinergic neurons are involved with reinforcement, and yet these cells have not been investigated with regard to the neurobiological mechanisms underlying opioid abuse. Results obtained in the proposed experiments should impart needed information on the neurobiology of the VP/nB, and also provide significant information useful in devising appropriate pharmacological strategies for the treatment of narcotic abuse.