ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

情感性疾病的主要特征之一是脑电活动中断 昼夜睡眠-觉醒周期，特征是睡眠不足，间歇性和 清晨醒着。伴随着这场骚乱的是异常现象。 在激素等生理过程的时间关系中 随着睡眠-觉醒周期的释放和温度调节。一 对情感性疾病阶段推进假说的预测是 重新建立更正常的时间相位关系 紊乱的昼夜节律可能导致抑郁症的缓解 症状学。抗抑郁剂化学治疗的机制可能是 与这一预测一致；以前的报告表明 锂和MAO抑制剂Clorgyline对哺乳动物的影响 昼夜节律系统因此，我们已经开始评估抗抑郁药 对啮齿动物昼夜节律系统的化学影响。这个项目有 有必要设计、建造和评估啮齿动物的昼夜节律 节律监测设备。此外，我们最近完成了 初步实验旨在阐明Clorgyline对 啮齿动物的昼夜节律系统。 到目前为止，我们的研究表明啮齿动物的昼夜节律设施正在进行 动物的昼夜节律模式类似于 其他地方控制的昼夜节律实验室。我们的药理研究 指示a)对仓鼠昼夜节律的直接或间接的clorgyline输入 起搏器和b)对仓鼠静息活动的Clorgyline修改 周而复始。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，抗抑郁药物对 啮齿动物的昼夜节律起搏器。我们目前的研究计划是 重复这些发现并扩大我们的观察范围以确定 脑脊液对昼夜节律系统的输入机制和部位(S)。

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.