NEUROBIOLOGY OF DEPRESSION

在过去的十年中，已经发现了40种或更多的肽 存在于哺乳动物大脑的神经元中。 许多情况下，肽共存 在同一个神经元与经典的递质已被描述。 我们 实验室正在研究共存的功能意义， 中枢神经系统中的肽和递质，使用行为 工具. 我们的方法是在突触后核中插入导管 含有神经末梢和突触后受体的通路， 神经肽和神经递质共存。 行为动作 所述递质、所述肽以及递质的组合， 肽，直接显微注射到突触后部位，然后 评估以测试行为效应之间的潜在相互作用， 的发射器和肽。 A）我们先前表明，胆囊收缩素（CCK）电位 多巴胺诱导的丘脑核运动过度，其中CCK和 多巴胺共存。 今年，分析了CCK拮抗剂的 阻断多巴胺能神经递质CCK调节的药理学特异性 功能 两次显微注射到脑桥核， 丙谷胺和苯并曲普的腹膜内全身注射 特异性阻断CCK增强多巴胺诱导的 核团的过度运动 这一发现表明， 临床上有用的CCK拮抗剂给药途径可以阻断 中枢CCK功能，提示CCK拮抗剂可能是新的 降低中脑边缘多巴胺能功能的抗精神病药物 通路 B）P物质（SP）、促肾上腺皮质激素释放因子（CRF）和 乙酰胆碱酯酶（Ach E）在背外侧 投射到大鼠前额皮质的被盖神经元。 胆碱能 激动剂，卡巴胆碱，微量注射到前额叶皮层，诱导了一个 类似于“拳击”的刻板运动行为。“SP增强 卡巴胆碱诱发的“拳击”“这三重的功能意义 因此，共存可能是一种肽的上调和一种肽的下调。 通过其他肽调节初级递质的功能。

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.