ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

啮齿动物昼夜节律系统的抗抑郁药理学

• 批准号: 4696549
• 负责人: W C DUNCAN
• 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/4696549
• 关键词: MAO inhibitors; antidepressants; body temperature regulation; circadian rhythms; hormone regulation /control mechanism; lithium; monitoring device; psychopharmacology; psychophysiology; sleep; wakefulness

One of the major features of affective illness is disruption of the circadian sleep-wake cycle characterized by loss of sleep, intermittent and early morning wakefulness. Accompanying this disturbance are abnormalities in the temporal relationship of physiological processes such as hormone release and temperature regulation with the sleep-wake cycle. One prediction of the phase advance hypothesis of affective illness is that re-establishment of more normal temporal phase relationships between disordered circadian rhythms may result in remission of depressed symptomotology. The mechanism of antidepressant chemical treatments may be consistent with this prediction; previous reports indicate the psychoactive medications lithium and the MAO inhibitor clorgyline affect the mammalian circadian system. We have therefore begun to evaluate antidepressant chemical effects on the rodent circadian system. This project has necessitated the design, construction, and evaluation of a rodent circadian rhythm monitoring facility. In addition, we have recently completed preliminary experiments designed to clarify clorgyline's precise effect on the rodent circadian system. Our studies to date demonstrate the rodent circadian facility is performing as designed; animals exhibit circadian patterns similar to those in controlled circadian laboratories elsewhere. Our pharmacological studies indicate a) direct or indirect clorgyline input to the hamster circadian pacemaker and b) clorgyline modification of the hamster rest-activity cycle. While this evidence is preliminary, we feel these data are currently the most compelling evidence of antidepressant chemical input to the rodent circadian pacemaker. Our current research plans are to replicate these findings and extend our observations to determine the mechanism and site(s) of clorgyline's input to the circadian system.

情感性疾病的主要特征之一是 昼夜睡眠-觉醒周期的特征是睡眠丧失，间歇性和 清晨的觉醒 伴随着这种干扰的是异常 在生理过程的时间关系中， 释放和温度调节与睡眠-觉醒周期。 一 对情感性疾病的相位推进假说的预测是， 重建更正常的时间相位关系， 昼夜节律紊乱可能导致抑郁症的缓解， 植物学 抗抑郁药化学治疗的机制可能是 与这一预测一致;先前的报告表明， 药物锂和单胺氧化酶抑制剂氯吉林影响哺乳动物 昼夜节律系统 因此我们开始评估抗抑郁药 对啮齿动物昼夜节律系统的化学影响。 这个项目 有必要设计，建造和评估啮齿动物的昼夜节律 心律监测设备。 此外，我们最近完成了 初步实验旨在阐明氯吉林的精确作用， 啮齿动物的昼夜节律系统 我们迄今为止的研究表明，啮齿动物昼夜节律设施正在执行 按照设计;动物表现出类似于 控制其他地方的昼夜节律实验室。 我们的药理学研究 指示a）对仓鼠昼夜节律的直接或间接氯吉林输入 起搏器和B）仓鼠静息-活动的氯吉林修饰 周期 虽然这些证据是初步的，但我们认为这些数据是 目前最令人信服的证据表明，抗抑郁剂的化学输入， 啮齿动物的昼夜节律起搏器。 我们目前的研究计划是 复制这些发现，并扩大我们的观察，以确定 氯吉林输入昼夜节律系统的机制和位点。