ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

我们之前曾假设，抗抑郁剂的作用机制 对慢性药物治疗的反应包括对哺乳动物的影响 昼夜节律系统这些影响可能包括对表达式的修改 最终控制中央时钟的频率和/或相位 所有昼夜节律的表达。改变频率或频率的治疗 中央时钟的相位可能会改变中央时钟的组织 钟。 在哺乳动物中，生物钟由两个耦合的振荡器组成。 一个振荡器控制体温，另一个振荡器控制体温 活动和休息。药物可能通过影响a)改变生物钟 振荡器控制温度，b)振荡器控制 活动-休息或c)两者兼而有之。在这个项目中，抗抑郁剂的效果 关于体温和活动-休息的日常模式的药物正在被 检查以确定抗抑郁药物如何影响夫妻 叙利亚仓鼠的振荡器系统。 A型单胺氧化酶a)的慢性抑制降低了频率 中央时钟b)相位延迟最低下丘脑温度， C)降低下丘脑温度水平叙利亚仓鼠和d) 减少快速眼动睡眠。抗抑郁药对5-羟色胺再摄取的抑制作用 氟西汀还可以降低下丘脑温度，减少快速眼动睡眠。 这表明5-羟色胺在慢性药物作用中起部分中介作用。 快速眼动睡眠水平和体温。这些观察结果提供了证据 具有不同药理特征的抗抑郁药物会改变 长期给药时的体温调节。这些药物的作用 在昼夜节律起搏器的表达上可能通过 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.