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:3845232
- 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:MAO inhibitors antidepressants biological clocks body temperature regulation brain circulation chlorpromazine circadian rhythms dopamine fluoxetine haloperidol hamsters hypothalamus lateral geniculate body light intensity lithium mental disorder chemotherapy neurochemistry psychopharmacology psychophysiology serotonin
项目摘要
We have hypothesized that the therapeutic mechanism of antidepressant
drugs depends on their effects on the circadian system. This hypothesis
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.
During the past year this project has focused on two major areas. One
area of investigation has been on the effects of chronic psychoactive
drug treatment on regulation of brain temperature. These experiments
indicate that chronic antidepressant drug treatment with clorgyline,
fluoxetine or lithium, lowers hypothalamic temperature, particularly
during the rest phase of the circadian cycle. In contrast, chronic
treatment with the neuroleptic drugs chlorpromazine or haloperidol
increase hypothalamic temperature. Further research is required to
understand the mechanisms through which these drugs alter hypothalamic
temperature. For example, it is possible that antidepressant drugs
decrease the set-point of hypothalamic temperature regulation, possibly
through their serotonergic properties. These drugs, through multiple
effects on circulating hormones and neurotransmitters, could also alter
hypothalamic temperature by changing blood flow to the hypothalamus. In
depressed patients, elevated body temperature is often observed during
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.
In light of the effects of antidepressant drugs on circadian variation of
hypothalamic temperature, a second area of research has been to determine
the chronic effects of clorgyline, an MAOI which a) chronically decreases
hypothalamic temperature in hamsters and b) delays the circadian
pacemaker, on brain monoamines in discrete brain nuclei reported to be
involved in circadian regulation of behavior and thermoregulation. These
studies indicate that chronic clorgyline treatment elevates serotonin
(5HT) levels in terminal regions of the hypothalamus (suprachiasmatic
nucleus, paraventricular nucleus, medial preoptic area) and thalamus
(lateral geniculate nucleus), and in cell bodies of the dorsal and median
raphe. It also elevates dopamine levels in the ventral tegmental area,
the caudate nucleus and the nucleus accumbens. Furthermore, in all
regions except the dorsal raphe nucleus and the suprachiasmatic nucleus,
clorgyline treatment eliminated the circadian rhythm of 5HT that is
normally present.
我们假设抗抑郁药的治疗机制
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:
5203704 - 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:
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:
5203726 - 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:
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:
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:
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:
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:
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:
3759410 - 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:
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