ORPHANIN FQ OPIOID INTERACTIONS IN THE REGULATION OF BRAIN REWARD SYSTEMS

孤啡肽-阿片相互作用在脑奖赏系统调节中的作用 阐明孤啡肽FQ调节活性的机制(S) 使用体内神经化学和原代培养的中脑边缘DA系统 培养电生理学结合免疫细胞化学/IN 原位杂交受体定位研究旨在发现 回答以下具体问题： A.观察到孤啡肽FQ对伏隔核多巴胺释放的抑制作用 静脉注射后进行微透析。多肽的给药，由于 腹侧被盖区(VTA)和/或伏隔核的活动 在其他DA终末区域也观察到类似的影响 杏仁核、尾状核和前额叶皮质？ B.孤啡肽FQ受体能否在轴突终末和/或 中脑DA神经元在脑切片和VTA初级神经元上的树突 培养的DA神经元？ C.如果培养的DA细胞上表达孤啡肽FQ受体，它们是 在电生理测试中起作用，如果是，对什么离子通道起作用 他们是结对的吗？ D.如果孤啡素FQ不直接作用于DA，神经元可以孤啡素FQ 受体在神经化学可识别的轴突终末可见 对伏隔核或伏隔核的输入，如利用谷氨酸的输入， GABA、P物质还是脑啡肽？ E.FQ中的孤儿是否影响这些递质在FQ中的释放 VTA或伏隔核和DO拮抗剂阻断这些递质 孤儿FQ对DA释放的影响？ 2.确定孤儿FQ与内源性的关系 阿片类物质在伏核-苍白球通路中的作用 神经化学和神经解剖学方法。 A.孤啡肽FQ是否调节脑啡肽的释放 静脉注射，伏隔内注射还是苍白球内注射？ B.相反，孤啡素在钯中的释放是否受阿片类药物的调节 受体激动剂？ C.孤弧因子FQ受体定位于轴突终末和/或 脑啡肽能伏隔-苍白球神经元的树突 主要是在钯的突触后？ 相反，阿片受体在孤儿FQ上的表达是阳性的吗 钯内的神经元突起？ 3.观察孤儿FQ给药对行为的影响 确定多巴胺和阿片系统在调节这些活动中的作用。 A.孤啡肽的局部给药是否进入VTA或核团 伏隔草本引起低速运动，其行为效应可逆 使用间接的多巴胺激动剂。行为效应可逆吗？ 用间接的多巴胺激动剂？ B.孤儿FQ诱导的空腹咀嚼行为是否被 选择性D1样和D2样受体激动剂和 敌手？ C.孤啡肽是否局部注射到VTA、伏隔核或 厌恶钯？ D.孤儿FQ是否抵消了阿片类药物和 精神刺激性药物注射到这些区域的位置偏爱 范例？

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?