ORPHANIN FQ OPIOID INTERACTIONS IN THE REGULATION OF BRAIN REWARD SYSTEMS

孤啡肽-阿片类药物在脑奖赏系统调节中的相互作用 为了阐明FQ调节活性的机制， 使用体内神经化学物质和主要的 电生理和免疫细胞化学联合培养法 原位杂交受体定位研究， 答复下列具体问题： a.是否观察到， 在i. c. v.施用肽后进行微透析，由于 腹侧被盖区（VTA）和/或伏隔核的作用，以及 在其他DA末端区域观察到类似的效应，如 杏仁核尾状核和前额叶皮层 B.轴突终末和/或轴突终末上是否可观察到FQ受体 中脑DA神经元的树突在脑切片或VTA原发性 培养的DA神经元 C.如果多巴胺受体在培养的DA细胞上表达， 在电生理测试中起作用，如果是的话， 他们是情侣吗？ D.如果FQ中的多巴胺不直接作用于DA能神经元， 受体在神经化学可识别的轴突末端上可见 VTA或丘脑核的输入，如利用谷氨酸的输入， GABA，P物质还是脑啡肽？ e. FQ中的孤儿药是否会影响这些递质在 腹侧被盖区或延髓核，这些递质的拮抗剂是否阻断 FQ对DA释放的影响？ 2.为了确定FQ中的Rg与内源性 阿片类药物在丘脑核-苍白球通路中的作用 神经化学和神经解剖学方法。 a.多巴胺FQ调节脑啡肽释放在钯以下 静脉注射，丘脑内还是苍白球内注射 B.相反，是否阿片类药物调节了钯中FQ的释放 受体激动剂？ C.位于轴突终末的FQ受体中的Arc 树突的脑啡肽能神经元苍白球神经元或他们是 主要是突触后的钯 D.相反地，阿片受体表达在阿片受体阳性的 神经元的突起 3.为了检测氟喹给药对大鼠行为学的影响， 确定DA和阿片系统在介导这些行动中的作用。 a.局部给予VTA或细胞核中的FQ是否 由于行为效应是可逆的， 间接DA受体激动剂u Mid是行为效应可逆 间接多巴胺激动剂吗 B.是否通过以下方法可以改善由唾液酸引起的咀嚼空洞行为 给予选择性D1样和D2样受体激动剂， 对手？ C. VTA、延髓核或 钯厌恶？ D. FQ中的多巴胺是否抵消了阿片类药物的奖励作用， 精神兴奋剂药物注射到这些区域的位置偏好 范式？

Orphanin FQ-opioid Interactions in the regulation of brain reward systems To elucidate the mechanism(s) by which orphanin FQ modulates the activity of the mesolimbic DA system using an in vivo neurochemical and primary culture electrophysiology approach together with immunocytochemical/in situ hybridization receptor localization studies directed at finding answers to the following specific questions: a. Is the orphanin FQ-induced inhibition of accumbens DA release, observed with microdialysis following i.c.v. administration of the peptide, due to an action in the ventral tegmental area (VTA) and/or nucleus accumbens and are similar effects observed in other DA terminal regions such as the amygdala, caudate and prefrontal cortex? b. Can orphanin FQ receptors be visualized on axonal terminals and/or dendrites of midbrain DA neurons in brain sections or on VTA primary cultured DA neurons? c. If orphanin FQ receptors are expressed on DA cells in culture are they functional in electrophysiological tests and, if so, to what ion channels are they coupled? d. if orphanin FQ does not act directly on DA neurons can orphanin FQ receptors be visualized on neurochemically identifiable axonal terminal inputs to the VTA or nucleus accumbens such as those utilizing glutamate, GABA, substance P or enkephalin? e. Does orphan in FQ influence the release of these transmitters in the VTA or nucleus accumbens and do antagonists to these transmitters block orphanin FQ effects on DA release? 2. To determine the relationship between orphanin FQ and endogenous opioids in the nucleus accumbens-pallidal pathway using a combination of neurochemical and neuroanatomical approaches. a. Does orphanin FQ modulate enkephalin release in the palladium following i.c.v., intra-accumbens or intra-pallidal injection? b. Conversely, is orphanin FQ release in the palladium regulated by opioid receptor agonists? c. Arc orphanin FQ receptors localized on the axonal terminals and/or dendrites of enkephalinergic accumbens-pallidal neurons or are they predominantly post-synaptic in the palladium? d. Conversely, are opioid receptors expressed on orphanin FQ-positive neuronal processes within the palladium? 3. To examine the behavioral effects of orphanin FQ administration and determine the role of DA and opioid systems in mediating these actions. a. Does local administration of orphanin FQ into the VTA or nucleus accumbens induce hypolocomotion as is the behavioral effect reversible with an indirect DA agonist. u Mid is the behavioral effect reversible with an indirect DA agonist? b. Is orphanin FQ-induced vacuous chewing behavior modified by administration of selective D1-like and D2-like receptor agonists and antagonists? c. Is orphanin FQ administered locally into the VTA, nucleus accumbens or palladium aversive? d. Does orphanin FQ counteract the rewarding effects of opiate and psychostimulant drugs injected into these regions in place-preference paradigms?