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:
  • 项目状态:
    未结题

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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W C DUNCAN的其他文献

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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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  • 批准号:
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