OPIOIDS AND THE PHYSIOLOGY OF THE VENTRAL PALLIDUM

苍白球腹侧核和基底核(Vp/Nb)是边缘脑区域 它们表现出高浓度的u、β和kappa阿片受体， 并由伏隔核的投射密集支配，这些投射包含 阿片肽。关于边缘的中心作用已有共识 内源性阿片类药物作用的系统和奖赏机制 关联于(例如)吸食海洛因。然而，特别的是 副总裁/副秘书长对这一角色的贡献尚不清楚。这是最基本的 缺陷是我们对VP/NB阿片类药物生理学缺乏了解。 当前竞争更新中的实验将通过以下方式填补这一空白 表征VP/NB阿片类药物的电生理药理 关注阿片类药物调节次级神经递质的倾向 包含在VP/NB的边缘传入神经中。为此，两位将军 具体目标将得到解决： 具体目标1是表征药物的电生理特性 Vp/NB神经细胞膜，并评价阿片类药物的药理作用 调节这些特性的受体亚型。现建议： Vp/NB中的神经元亚群可能表现出不同的药理作用 阿片类药物给药的资料。为了解决这一假设，一个新的 将描述发育的VP/NB神经元并将其与神经元相关联 通过免疫组织化学标记物识别的亚群 主要的躯体传输器。随后的实验将详细说明 阿片受体的药理学-亚型，确定离子电导 被阿片类药物改变，并检查阿片类激动剂改变 这些神经元亚群的突触前和/或突触后事件。 特定目标2寻求表征阿片类药物对递质的调制 系统在VP/NB内融合。建议VP/NB阿片类药物 具有修改传入信号检测门限的能力 以及这些输入影响的信噪比。至 测试这些假说，将使用体内电生理程序 其中单个神经元被细胞外监测。阿片类调制 信号增益的影响将通过比较 离子电泳法应用阿片类药物对其他物质引起的活动的影响 递质与阿片类药物对自发活动的影响。另外， Vp/NB的突出边缘传入将受到电刺激， 以及(1)伏隔核条件反射的能力(释放 内源性阿片类药物)，以及(2)离子电泳法应用的阿片类药物 将确定在VP/NB中引起的影响响应。这将是 提示VP/NB阿片类物质是否能调节激活的突触效应 投入。 以这两个具体目标为指导的研究将评估 神经元水平上的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 大大加深了我们对VP/NB阿片类药物功能的理解，并提供了一种 为未来关于副总统/毒品局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.