ANTIDEPRESSANT PHARMACOLOGY OF THE RODENT CIRCADIAN SYSTEM
啮齿动物昼夜节律系统的抗抑郁药理学
基本信息
- 批准号:5203704
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:antidepressants antipsychotic agents body physical activity body temperature body temperature regulation brain metabolism chordate locomotion circadian rhythms cortisol drug administration rate /duration hamsters hypothalamus lighting neurochemistry neurotransmitter metabolism oxygen consumption photobiology psychobiology psychopharmacology serotonin
项目摘要
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.
抗抑郁药物的治疗机制可能包括其作用机制
对昼夜节律系统的影响。这一可能性正在由
检测抗抑郁药和抗精神病药物对精神状态的影响
控制日常运动节奏的昼夜节律起搏器,
体温和脑电睡眠。
我们最近的调查集中在慢性疾病的影响上。
精神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
起搏器以及调节体温的中央恒温器。
这些实验表明,抗抑郁药物和抗精神病药物
药物分别增加和减少,昼夜节律幅度
下丘脑温度。更具体地说,慢性抗抑郁药物
治疗降低休息期间的下丘脑温度(光)
相位。抗精神病药物(氯丙嗪和氟哌啶醇)增加
静息时的下丘脑温度。
下丘脑降温可能涉及下丘脑的5-羟色胺能特性。
毒品。抗抑郁药物可能通过以下途径改变下丘脑温度
脑底动脉血流或静脉引流的改变
下丘脑。事实上,每一种抗抑郁药物
降低了Th,但有些未能使Th的昼夜节律延迟,
这表明前者可能与
抗抑郁作用机制优于后者。在抑郁症患者中,
夜间休息时体温经常升高,而且
抑郁症的药物治疗和非药物治疗有
据报道会降低体温。因此,这一发现
抗抑郁药物降低下丘脑温度可能很重要
了解它们的治疗机制。
与对照组相比,接受药物治疗的仓鼠更喜欢温暖的环境温度,
表明仓鼠正在利用行为体温调节来
补偿药物引起的Th下降。抗抑郁药
降低下丘脑温度(Th),但不是测量的设定点
通过静息耗氧量。这两个观察结果,以及
观察到药物中的皮质醇和运动活动水平增加
经过治疗的仓鼠,表明药物治疗可能会激活寒冷防御
机制。
调查的第二个领域是确定
5-羟色胺也参与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
5-羟色胺的变异。光照对所测5-羟色胺水平的影响分析
在离散的大脑核团中表明5-羟色胺水平在终末升高
在急性光照射期间,细胞内没有这种细胞,而是某些区域。数据
提示光照对5-羟色胺代谢有不同的影响
大脑区域。
项目成果
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{{ truncateString('W C DUNCAN', 18)}}的其他基金
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:
2578714 - 财政年份:
- 资助金额:
-- - 项目类别:
EFFECT OF ANTIDEPRESSANT DRUGS ON SENSITIVITY OF THE CIRCADIAN PACEMAKER
抗抑郁药物对昼夜节律起搏器敏感性的影响
- 批准号:
6162879 - 财政年份:
- 资助金额:
-- - 项目类别:
EFFECT OF ANTIDEPRESSANT DRUGS ON SENSITIVITY OF THE CIRCADIAN PACEMAKER
抗抑郁药物对昼夜节律起搏器敏感性的影响
- 批准号:
5203726 - 财政年份:
- 资助金额:
-- - 项目类别:
CHEMICAL ANTIDEPRESSANT EFFECTS ON BODY MASS AND BODY COMPOSITION IN HAMSTERS
化学抗抑郁药对仓鼠体重和身体成分的影响
- 批准号:
3880933 - 财政年份:
- 资助金额:
-- - 项目类别:
CHEMICAL ANTIDEPRESSANT EFFECTS ON BODY MASS AND BODY COMPOSITIION IN HAMSTERS
化学抗抑郁药对仓鼠体重和身体成分的影响
- 批准号:
3944832 - 财政年份:
- 资助金额:
-- - 项目类别:
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 - 财政年份:
- 资助金额:
-- - 项目类别:
CHEMICAL ANTIDEPRESSANT EFFECTS ON BODY MASS AND BODY COMPOSITION IN HAMSTERS
化学抗抑郁药对仓鼠体重和身体成分的影响
- 批准号:
3859922 - 财政年份:
- 资助金额:
-- - 项目类别:
EFFECT OF ANTIDEPRESSANT DRUG ON SENSITIVITY OF THE CIRCADIAN PACEMAKER
抗抑郁药物对昼夜节律起搏器敏感性的影响
- 批准号:
3781406 - 财政年份:
- 资助金额:
-- - 项目类别:
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:
3845232 - 财政年份:
- 资助金额:
-- - 项目类别:
EFFECT OF ANTIDEPRESSANT DRUG ON SENSITIVITY OF THE CIRCADIAN PACEMAKER
抗抑郁药物对昼夜节律起搏器敏感性的影响
- 批准号:
3845266 - 财政年份:
- 资助金额:
-- - 项目类别:
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