BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

神经肽的行为功能

• 批准号: 3921934
• 负责人: J N CRAWLEY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3921934
• 关键词: Alzheimer's disease; acetylcholine; adrenergic agents; anticholinergic agent; brain mapping; brain metabolism; cerebral ventricles; cholecystokinin; chordate locomotion; disease /disorder model; dopamine; drug interactions; hippocampus; hormone inhibitor; laboratory rat; limbic system; microinjections; mood disorders; muscarinic receptor; neural information processing; neurons; neuropeptide receptor; neuropeptides; neuropharmacology; neurotransmitters; nucleus accumbens; radioimmunoassay; substantia innominata; tegmentum

A. Microinjection of the CCK antagonist, proglumide, in the nucleus accumbens of rats, partially blocked hyperlocomotion in a darkened Digiscan activity monitor. This finding is the first evidence that endogenous CCK contributes to mesolimbic functions. B. Characterization of the ventral tegmental pharmacology of CCK found that CCK modulated DA, i.e. CCK had no effect alone, but potentiated DA-induced hypolocomotion, when microinjected into the VTA. This effect was mimicked by unsulfated CCK-8. and by CCK-4. and was not blocked by proglumide, suggesting mediation by a central-type CCK receptor subtype. A central-type CCK agonist mimicked this effect. C. Galanin is a 29-amino acid peptide which coexists with acetylcholine in the septo-hippocampal pathway of the rat. Intraventricular or intrahippocampal microinjection of nanogram doses of galanin blocked the ability of acetylcholine to reverse memory deficits on a t-maze delayed alternation task in rats lesioned in the nucleus basalis of Meynert-medial septal area. An antagonist of this inhibitory peptide is being sought as a possible approach for the treatment of some cognitive dysfunctions associated with Alzheimers disease. D. Microdialysis for neuropeptides is being developed using different plastics which allow greater passage of the large, highly charged peptides. Radioimmunoassays have detected measurable levels of cholecystokinin in the nucleus accumbens, and measurable levels of galanin in the ventral hippocampus, of anesthetized rats.

A. CCK 拮抗剂丙谷胺的显微注射 大鼠伏隔核部分阻断过度运动 变暗的 Digiscan 活动监视器。 这个发现是第一个 有证据表明内源性 CCK 有助于中脑边缘功能。 B. CCK 腹侧被盖药理学特征 发现CCK调节DA，即CCK单独没有作用，但是 当将 DA 显微注射到 VTA。 未硫酸化的 CCK-8 模仿了这种效果。和CCK-4。 并且没有被丙谷胺阻断，表明由 中枢型CCK受体亚型。 中枢型 CCK 激动剂 模仿了这个效果。 C. 甘丙肽是一种 29 个氨基酸的肽，与 大鼠隔膜-海马通路中的乙酰胆碱。 脑室内或海马内微注射纳克 一定剂量的甘丙肽可阻断乙酰胆碱逆转的能力 大鼠 T 迷宫延迟交替任务的记忆缺陷 病变位于 Meynert 内侧间隔区的基底核。 一个 正在寻找这种抑制肽的拮抗剂作为可能的药物 治疗某些认知功能障碍的方法 与阿尔茨海默病有关。 D. 正在开发神经肽微透析 不同的塑料允许更大的、高度的通过 带电荷的肽。 放射免疫分析检测到 伏隔核中胆囊收缩素的水平，并且可测量 麻醉大鼠腹侧海马甘丙肽的水平。