ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

我们先前假设抗抑郁药的作用机制 对慢性药物治疗的反应包括对哺乳动物 昼夜节律系统这些影响可能包括表达式中的修改 频率和/或相位的中央时钟，最终控制 所有昼夜节律的表达。改变频率的治疗或 中央时钟的相位可能会改变中央时钟的组织。 时钟 在哺乳动物中，生物钟是由两个耦合的振荡器组成的。 一个振荡器控制体温，第二个振荡器控制 活动和休息。药物可以通过影响a） 振荡器控制温度，B）振荡器控制温度， 活动-休息或C）两者。在这个项目中， 药物对体温和活动-休息的日常模式正在 为了确定抗抑郁药物如何影响耦合 叙利亚仓鼠的振荡器系统。 A型单胺氧化酶的慢性抑制a）降低了 B）相位延迟最低下丘脑温度， c）降低叙利亚仓鼠下丘脑温度的水平，和d） 减少REM睡眠。抗抑郁药对5-HT再摄取的抑制作用 氟西汀还可降低下丘脑温度并减少REM睡眠。 这表明，5-HT介导了部分慢性药物作用， 快速眼动睡眠水平和体温。这些观察提供了证据 具有不同药理学特征的抗抑郁药物 长期服用时的体温调节。这些药物的效果 对昼夜节律起搏器表达的影响可能与 它们对控制体温的振荡器的影响

We have previously hypothesized that the mechanism of the antidepressant response to chronic drug therapy includes effects on the mammalian circadian system. These effects may include modifications in the expression of frequency and/or phase of the central clock that ultimately controls the expression of all circadian rhythms. Treatments that alter the frequency or phase of the central clock may change the organization of the central clock. In mammals, the circadian clock is organized as two coupled oscillators. One oscillator controls body temperature, a second oscillator controls activity and rest. Drugs may alter the circadian clock by affecting a) the oscillator controlling temperature, b) the oscillator controlling activity-rest or c) both. In this project, the effects of antidepressant drugs on the daily patterns of body temperature and activity-rest are being examined in order to determine how antidepressant drugs affect the coupled oscillator system of Syrian hamsters. Chronic inhibition of type A monoamine oxidase a) decreases the frequency of the central clock b)phase-delays the minimum hypothalamic temperature, c) decreases the level of hypothalamic temperature Syrian hamsters and d) reduces REM sleep. Inhibition of 5HT reuptake with the antidepressant drug fluoxetine also decreases hypothalamic temperature and reduces REM sleep. This suggests that 5HT mediates part of the chronic drug effects on the level of REM sleep and temperature. These observations provide evidence that antidepressant drugs with distinct pharmacological profiles alter thermoregulation when administered chronically. The effects of these drugs on the expression of the circadian pacemaker may possibly be linked by their effects on the oscillator that controls body temperature.