ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM

抗抑郁药物的治疗机制可能包括其 对昼夜节律系统的影响。这一可能性正在研究中， 测试抗抑郁药和神经安定药对 昼夜节律起搏器控制运动活动的日常节奏， 体温和脑电图睡眠。 我们最近的研究集中在慢性 精神活性药物治疗对体温昼夜节律的影响 在下丘脑中，包含昼夜节律的大脑区域 心脏起搏器以及调节体温的中央恒温器。 这些实验表明，抗抑郁药和神经安定药 药物分别增加和减少， 下丘脑温度 更具体地说，慢性抗抑郁药 治疗降低休息期间的下丘脑温度（光） 相位精神抑制药（氯丙嗪和氟哌啶醇）增加 下丘脑温度在休息阶段。 下丘脑冷却可能涉及下丘脑的多巴胺能特性。 毒品抗抑郁药可通过以下方式改变下丘脑温度： 改变基底部的脑动脉血流或静脉引流 下丘脑 事实上每种抗抑郁药 降低Th，但有些未能使Th的日节律相延迟， 这表明，前者可能更密切相关的 抗抑郁机制优于后者。 在抑郁症患者中， 夜间休息时经常观察到体温升高， 抑郁症的药物和非药物治疗 据报道可以降低体温 因此， 抗抑郁药物降低下丘脑温度可能很重要 了解其治疗机制。 药物处理的仓鼠比对照组更喜欢温暖的环境温度， 表明仓鼠正在利用行为体温调节 补偿药物诱导的Th减少。 抗抑郁药物 降低下丘脑温度（Th），但不降低测量的设定点 通过休息时的耗氧量这两个观察，以及 观察到皮质醇和运动活动水平增加药物 这表明药物治疗可能会激活寒冷防御， 机制等 第二个调查领域是确定 5-羟色胺调节昼夜节律系统对光的反应， 相反的关系：光在调节昼夜节律中的作用 血清素的变异 分析光对测量的5 HT水平的影响 在离散的脑核团中，表明5 HT水平在终末增加 区域，但不是在细胞体在急性光暴露。 数据 表明光照对不同组织中5 HT代谢的影响不同， 大脑区域。

The therapeutic mechanism of antidepressant drugs possibly includes their effects on the circadian system. This possibility is being examined by testing the effects of antidepressant and neuroleptic drugs on the state of the circadian pacemaker that controls daily rhythms of motor activity, temperature and EEG sleep. Our recent investigations have focused on the effects of chronic psychoactive drug treatment on the circadian pattern of temperature within the hypothalamus, the brain region containing the circadian pacemaker as well as central thermostat which regulates body temperature. These experiments have shown that antidepressant drugs and neuroleptic drugs increase and decrease respectively, the circadian amplitude of hypothalamic temperature. More specifically, chronic antidepressant drug treatments decrease hypothalamic temperature during the rest (light) phase. The neuroleptic drugs (chlorpromazine and haloperidol) increase hypothalamic temperature during the rest phase. Hypothalamic cooling is likely to involve serotonergic properties of the drugs. Antidepressant drugs may alter hypothalamic temperature by changing cerebral arterial blood flow or venous drainage at the base of the hypothalamus. The fact that each of the antidepressant drugs decreased Th, but some failed to phase-delay the daily rhythm in Th, suggests that the former may be more closely associated with the antidepressant mechanism than the latter. In depressed patients, elevated body temperature is often observed during nocturnal rest, and pharmacological and non-pharmacological treatments of depression have been reported to lower body temperature. Therefore, the findings that antidepressant drugs decrease hypothalamic temperature may be important in understanding their therapeutic mechanism. Drug-treated hamsters prefer warmer ambient temperatures than controls, indicating the hamsters are utilizing behavioral thermoregulation to compensate for the drug-induced decrease in Th. Antidepressant drugs decrease hypothalamic temperature (Th), but not the set-point as measured by resting oxygen consumption. These two observations, as well as the observations that cortisol and motor activity levels increase in drug treated hamsters, suggests that drug treatment may activate cold defense mechanisms. A second area of investigation has been to determine the role of serotonin in modulating the circadian system response to light, as well as the reverse relationship: the role of light in modulating circadian variation of serotonin. Analysis of light effects on 5HT levels measured in discrete brain nuclei indicates that 5HT levels increase in terminal regions but not in cell bodies during acute light exposure. The data suggest that light differentially affects 5HT metabolism within different brain regions.