EFFECT OF ANTIDEPRESSANT DRUGS ON SENSITIVITY OF THE CIRCADIAN PACEMAKER

昼夜节律的时间由位于 在视交叉上核(SCN)。暴露于a)光和b) 5-羟色胺能激动剂，重置时钟的计时和模式 由时钟控制的行为。其生理特性和 临床抗抑郁药物对神经通路的影响 光照和5-羟色胺对昼夜节律和季节生物的影响 目前正在研究仓鼠的节律。 在第一系列实验中，生物行为测试已经被用来 评估抗抑郁药物对精神分裂症敏感性的影响 调节对光的夹带的视觉通路。MAOI、CLOGYLINE和 锂，降低视觉通路调节的敏感性 用光进行位相重置。这种反应在clorgyline过程中降低 治疗与5-羟色胺能药物的可能性一致 减少用光重置位相的幅度。 MAOI，clorgyline的慢性治疗，通过 5-羟色胺激动剂8-OH-DPAT和苯二氮卓类三唑仑。DPAT诱导 氯吉林治疗的仓鼠的相移比对照组的要小 提示5-羟色胺受体可能具有脱敏作用。减少的 注射5HT1A型激动剂和阿司匹林后的相移反应 苯二氮类药物，表明慢性抗抑郁药物可能会减少 行为对生物钟的反馈效应。 在第二系列实验中，抗抑郁药物对 光诱导即刻早期基因c-fos的研究正在进行中。二 问题正在得到解决。第一，是否接受慢性氯吉林治疗 减少光诱导的c-fos表达？第二，是 C-fos基因表达受时间推进和细胞周期的影响相似 光的相位延迟效应？在亚慢性氯吉林治疗期间 SCN细胞内c-fos表达减少。50%的人 C-fos表达细胞的减少与c-fos基因表达减少50%是一致的。 慢性阻塞性肺疾病患者的位相重置反应的大小 克洛吉林治疗过的仓鼠。

The timing of circadian rhythms is regulated by a circadian clock located in the suprachiasmatic nucleus (SCN). Exposure to a) light and b) serotonergic agonists, resets the timing of the clock and the pattern of behaviors controlled by the clock. The physiological properties and clinical antidepressant drugs effects, on neural pathways that mediate the effects of light and serotonin on circadian and seasonal biological rhythms are being investigated in hamsters. In the first series of experiments, a biobehavioral assay has been used to assess the effects of antidepressant drugs on the sensitivity of the visual pathway mediating entrainment to light. The MAOI, clorgyline, and lithium, decreases the sensitivity of the visual pathway mediating phase-resetting by light. This decreased response during clorgyline treatment is consistent with the possibility that serotonergic agents decrease the magnitude of phase-resetting by light. Chronic treatment with the MAOI, clorgyline, alters phase-resetting by the 5HT agonist 8 OH DPAT, and by the benzodiazepine triazolam. DPAT-induced phase-shifts are smaller in clorgyline-treated than control hamsters suggesting possible desensitization of 5HT receptors. The decreased phase-shifting response following injections by a 5HT 1A agonist and a benzodiazepine, indicates that chronic antidepressant drugs may diminish the feedback effects of behavior on the circadian clock. In a second series of experiments, the effect of antidepressant drugs on light induction of the immediate early gene c-fos is being examined. Two questions are being addressed. First, does chronic clorgyline treatment decrease light-induced c-fos expression? Second, is the magnitude of c-fos expression affected similarly by the phase-advancing and phase-delaying effects of light? During subchronic clorgyline treatment there is a decrease in c-fos expression within SCN cells. The 50% decrease in cells expressing c-fos is consistent with the 50% decrease in the magnitude of the phase-resetting response to light in chronic clorgyline-treated hamsters.