NEUROBIOLOGY OF DEPRESSION

在过去的十年里，已经发现了四十多种多肽 定位于哺乳动物大脑的神经元。多肽共存的多个病例 与经典神经递质相同的神经元中的神经递质已被描述。我们的 实验室正在研究共存的功能意义 中枢神经系统中的多肽和递质，使用行为 工具。我们的方法包括插入突触后核 含有神经末梢和突触后受体的通路 哪些神经肽和神经递质共存。的行为行为 递质、肽以及递质和递质的组合 肽(S)，直接显微注射到突触后部位，然后 评估以测试行为影响之间的潜在交互作用 递质和多肽的关系(S)。 A)我们之前已经证明了CCK电位 多巴胺引起伏隔核超运动，CCK和 多巴胺共存。今年，CCK的拮抗者被分析为他们的 阻断多巴胺能CCK调控的药理特异性 功能。伏隔核内微量注射和 丙谷胺和苯曲普钠腹膜腔内全身注射 特异性阻断CCK增强多巴胺诱导的能力 伏隔核的过度运动。这一发现表明，一个 临床上有用的CCK拮抗剂给药途径可以阻断 CCK的中枢作用，提示CCK拮抗剂可能是新的 抗精神病药降低中脑边缘多巴胺能神经功能 路径。 B)P物质(SP)、促肾上腺皮质激素释放因子(CRF) 乙酰胆碱酯酶(Ach E)在背外侧区共存 投射到大鼠前额叶皮质的被盖神经元。胆碱能 激动剂，卡巴胆碱，微量注射到前额叶皮质，诱导出 类似于“拳击”的深刻刻板印象的运动行为。SP增强型 卡巴胆碱诱导的“拳击”。这个三元组的功能意义 因此，共存可能是一种肽的上调和一种肽的下调。 另一种多肽对初级递质功能的调节。

The past decade has witnessed the discovery of forty or more peptides localized in neurons of mammalian brain. Many cases of peptides coexisting in the same neuron with classical transmitters have been described. Our laboratory is investigating the functional significance of coexisting peptides and transmitters in the central nervous system, using behavioral tools. Our approach involves cannulating the postsynaptic nucleus containing the nerve terminals and postsynaptic receptors of pathways in which neuropeptides and neurotransmitters coexist. Behavioral actions of the transmitter, the peptide, and combinations of transmitters and peptide(s), microinjected directly into the postsynaptic site, and then evaluated to test for potential interactions between the behavioral effects of the transmitter and the peptide(s). A) We previously showed that cholecystokinin (CCK) potential dopamine-induced hyperlocomotion in the nucleus accumbens, where CCK and dopamine coexist. This year, antagonists of CCK were analyzed for their pharmacological specificity in blocking the CCK modulation of dopaminergic function. Both microinjections into the nucleus accumbens and intrapertitoneal systemic injections of proglumide and benzotript specifically blocked the ability of CCK to potentiate dopamine-induced hyperlocomotion in the nucleu accumbens. This finding demonstrates that a clinically useful route of administration of a CCK antagonist can block central CCK function, suggesting that CCK antagonists may be novel antipsychotic agents in reducing dopaminergic function in the mesolimbic pathway. B) Substance P (SP), corticotropin releasing factor (CRF) and acetylcholinesterase (Ach E) were found to coexist in dorsolateral tegmental neurons projecting to the rat prefrontal cortex. The cholinergic agonist, carbachol, microinjected into the prefrontal cortex, induced a profound stereotyped motor behavior resembling "boxing." SP potentiated carbachol-induced "boxing." The functional significance of this triple coexistence, therefore, may be an upregulation by one peptide, and a down regulation by the other peptide, of the function of the primary transmitter.