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，使用了生物行为分析 S对抗抑郁药物敏感性的影响 调节对光的夹带的视觉通路。MAOI，CLOGYLE，但是 而不是锂，会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。这不太可能 因此，单一的视觉特性，即视觉降低 携带途径的敏感性，是临床研究的基础 这两种药物的抗抑郁性能。然而，不同的效果 两种药物对视觉敏感度的影响可能与不同有关 药物的昼夜节律和情绪稳定作用。 MAOI，clorgyline，慢性治疗通过改变相位重置 5-羟色胺激动剂8-OH-DPAT和苯二氮卓类三唑仑。DPAT- Clorgyline处理组的诱导相移小于对照组 仓鼠提示5-羟色胺受体可能脱敏。这个 注射5HT1A后相移反应减弱 激动剂和苯二氮卓类，表明慢性抗抑郁药物 可能会减弱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，c-的大小 Fos的表达受阶段推进和阶段-时间的影响相似 延缓光线的影响？在亚慢性Clorgyline治疗期间 是SCN细胞内c-fos表达的减少。减少了50% 在细胞中表达c-fos与c-fos基因表达减少50%相一致 慢性脉络膜对光的位相重置反应的大小 治疗过的仓鼠。目前正在分析更多数据。 目前的实验正在检测光的位相重置效应。 在长(夏季)和短(冬季)光周期中饲养的仓鼠。 初步结果表明，长期暴露在短时间内 光周期增加了光诱导相移的幅度 相对于夏季光周期曝光量。我们正在检查的水平 光诱导c-fos在短光和长光周期中的诱导以及 抗抑郁药物降低时相-幅度的能力 变化的反应。

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 effect s of antidepressant drugs on the sensitivity of the visual pathway mediating entrainment to light. The MAOI, clorgyline, but not 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. It is unlikely therefore, that a single visual property, i.e. decreased visual sensitivity of the entrainment pathway, underlies the clinical antidepressant property of the two drugs. However, the different effects of the two drugs on visual sensitivity may be related to the different circadian and mood stabilizing effects of the drugs. 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 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 the 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. Additional data are currently being analyzed. Current experiments are examining the phase-resetting effects of light in hamsters housed in long (summer) and short (winter) photoperiods. Preliminary results indicate that prolonged exposure to a short photoperiod increases the magnitude of light-induced phase-shifts relative to summer photoperiod exposure. We are examining the level of light-induced c-fos induction in short and long photoperiods, as well as the capacity of antidepressant drugs to decrease the magnitude of phase- shifting response.