OPIOIDS AND THE PHYSIOLOGY OF THE VENTRAL PALLIDUM

腹侧苍白球和基底核（VP/nB）是边缘脑区 显示出高浓度的μ，δ和κ阿片受体， 并由延髓核投射密集支配， 阿片肽 关于大脑边缘系统的中心作用， 内源性阿片样物质和奖赏机制的功能系统 相关（例如）海洛因管理 然而，具体 VP/nB对这一角色的贡献尚不清楚。 这其中的根本 不足之处在于我们对VP/nB阿片生理学缺乏了解。 目前的竞争性更新实验将填补这一空白， 表征VP/nB阿片类药物的电生理药理学， 关注阿片类药物调节二级神经递质的倾向 包含在VP/nB的边缘系统传入中。 为此，两位将军 具体目标如下： 具体目标1是表征 VP/nB神经元膜，并评价阿片类药物的药理学 调节这些特性的受体亚型。 拟将 VP/nB中的神经元亚群可能表现出不同的药理学作用， 阿片类药物给药的特征 为了解决这个问题，一个新的 将描述发育的VP/nB神经元，并将其与神经元相关。 通过免疫组织化学标记鉴定的亚群 主要的躯体递质。 随后的实验将详细说明 阿片受体亚型药理学，确定离子电导 阿片类药物改变，并检查阿片类药物激动剂改变 这些神经元亚群的突触前和/或突触后事件。 具体目标2旨在表征阿片类药物对递质的调节 系统在VP/nB中融合。 建议VP/nB阿片类药物 有能力改变传入信号的检测阈值 以及这些输入影响的信噪比关系。 到 为了验证这些假设，将使用体内电生理程序 其中单个神经元在细胞外被监测。 阿片调节 将通过比较以下因素的影响来检查信号增益 电离子透入应用的阿片类药物对其他引起的活动的影响 递质与阿片类药物对自发活动的影响。 此外，本发明还 VP/nB的显著边缘传入将被电刺激， 和能力（1）神经核调节（释放 内源性阿片样物质），和（2）离子电渗应用的阿片样物质， 将确定VP/nB中诱发的影响反应。 这将 表明VP/nB阿片类药物是否可以调节激活的突触功效 输入。 由这两个具体目标指导的研究将评估 神经元水平VP/nB阿片受体亚型的生理学 膜和完整的电路。 这些努力将有助于 基本上我们了解VP/nB阿片样物质的功能，并提供了一个 为未来VP/nB参与阿片类药物滥用的工作奠定基础。

The ventral pallidal and nucleus basalis (VP/nB) are limbic brain regions that exhibit high concentrations of mu, delta and kappa opioid receptors, and are densely innervated by nucleus accumbens projections that contain opioid peptides. A consensus exists regarding the central role of limbic systems in the function of endogenous opioids and reward mechanisms associated with (e.g.) heroin administration. However, the particular contribution of the VP/nB to this role is not known. Fundamental to this deficit is our lack of understanding of VP/nB opioid physiology. Experiments in the present competitive renewal will fill this gap by characterizing the electrophysiological pharmacology of VP/nB opioids, with focus on the propensity of opioids to modulate secondary neurotransmitters contained in limbic afferents to the VP/nB. To that end, two general Specific Aims will be addressed: Specific Aim 1 is to characterize the electrophysiologic properties of VP/nB neuronal membranes, and to evaluate the pharmacology of opioid receptor subtypes that regulate these properties. It is proposed that neuronal subpopulations in the VP/nB may exhibit distinct pharmacologic profiles to opioid administration. To address this hypothesis, a newly developed VP/nB neurons will be described and correlated to neuronal subpopulations identified via immunohistochemical markers for the predominant somatic transmitters. Subsequent experiments will detail the pharmacology of opioid receptor-subtypes, identify the ionic conductances altered by opioids, and examine the ability of opioid agonists to alter presynaptic and/or postsynaptic events for these neuronal subpopulations. Specific Aim 2 seeks to characterize opioid modulation of transmitter systems converging within the VP/nB. It is proposed that VP/nB opioids have the capacity to modify the threshold of detection of afferent signals as well as the signal-to-noise relationship of these input influences. To test these hypotheses, in vivo electrophysiological procedures will be used in which single neurons are monitored extracellularly. Opioid modulation of signal gain will be examined by comparing the effects of iontophoretically applied opioids on activity elicited by other transmitters versus opioid effects on spontaneous activity. Additionally, prominent limbic afferents to the VP/nB will be electrically stimulated, and the ability of (1) nucleus accumbens conditioning (which releases endogenous opioids), and (2) iontophoretically applied opioids, to influence responses evoked in the VP/nB will be ascertained. This will indicate if VP/nB opioids can modulate the synaptic efficacy of activated inputs. The studies directed by these two Specific Aims will evaluate the physiology of VP/nB opioid receptor-subtypes at the level of the neuronal membrane and the intact circuit. Such efforts will contribute substantially to our understanding of VP/nB opioid function, and provide a foundation for future work on VP/nB involvement in opioid abuse.