EFFECT OF ANTIDEPRESSANT DRUG ON SENSITIVITY OF THE CIRCADIAN PACEMAKER

在这个项目中，我们研究了神经的生理特性。 调节光对每日和远期时间影响的通路 季节性生物节律。这些节奏的时间是由 位于视交叉上核的生物钟。暴露于 Fight重置时钟的计时和行为模式 由时钟控制。本研究主要从两个方面展开。第一, 我们研究了光脉冲的时钟相位重置特性。 不同强度和持续时间的无毒动物。第二，我们 检查慢性抗抑郁药物治疗对时钟的影响 光的位相重置特性。有三个主要的发现 这些最近的调查。 首先，我们证实在没有药物的仓鼠中，光敏感度 这一途径在整个昼夜节律周期中是恒定的。那是, 在不同昼夜节律阶段传递的等量光量 产生的相移是每个阶段最大响应的50%。 其次，这些实验表明，慢性药物治疗 抗抑郁药物clorgyline降低了对光的敏感性， 这种效应的大小取决于昼夜节律的相位。 光线传递的周期。因此，需要更多的光线来 对晚光产生50%的相移响应，而不是产生50% 对晨光的反应。敏感的日常模式的转变 光可能有助于这种药物的抗抑郁性能。 目前正在研究这种敏感度变化的机制。 这种药物可能会随着时间的推移改变光的整合。 第三，尽管之前发表的报告表明锂会改变 用眼电图仪测量的视觉反应和 神经生理学技术，我们最近的数据表明锂 不能改变感光材料的灵敏度或响应性 夹带途径。这些结果强调了这样一种观点，即 负责携带昼夜节律的系统是 与其他视觉系统分开。例如，光学系统 中介夹带具有较高的响应阈值(约6个对数单位 高于视觉阈值)，并将光刺激积分高达45 几分钟(相比之下，一些杆状感光器只有1-3秒)。这个 锂改变视觉反应，但不改变夹带反应的事实 强调有必要对此进行进一步的研究 独特而清晰的光学系统。

In this project we investigate the physiological properties of the neural pathways that mediate the effect of light on the timing of daily and seasonal biological rhythms. The timing of these rhythms is regulated by a circadian clock located in the suprachiasmatic nucleus. Exposure to fight resets the timing of the clock and the pattern of behaviors controlled by the clock. There are two aspects of this research. First, we examine the clock phase-resetting properties of light-pulses of different intensities and durations in drug-free animals. Second, we examine the effects of chronic, antidepressant drug treatments on clock phase-resetting properties of light. There are three major findings of these recent investigations. First, we confirmed that in drug-free hamsters, the photic sensitivity of this pathway is constant throughout the circadian cycle. That is, equivalent quantities of light delivered at different circadian phases produce phase-shifts that are 50% of the maximum response at each phase. Second, these experiments demonstrate that chronic treatment with the antidepressant drug, clorgyline, decreases sensitivity to light, and that the magnitude of this effect is dependent upon the phase of the circadian cycle at which light is delivered. Thus, more light is required to produce a 50% phase-shift response to evening light than to produce a 50% response to morning light. The shift in the daily pattern of sensitivity to light may contribute to the antidepressant properties of this drug. The mechanism of this shift in sensitivity is currently being examined. The drug may alter the integration of light over time. Third, although previously published reports indicate that lithium alters visual responses as measured by electrooculographic and neurophysiological techniques, our recent data suggests that lithium fails to alter the sensitivity or responsiveness of the photic entrainment pathway. These results underscore the view that this photic system, which is responsible for the entrainment of circadian rhythms, is separate from other visual systems. For example, the photic system mediating entrainment has a high response threshold (about 6 log units above the threshold for vision) and integrates light stimuli for up to 45 minutes (in contrast to 1-3 seconds for some rod photoreceptors). The fact that lithium alters visual responses, but not entrainment responses to light underscores the need to conduct further research on this specific and distinct photic system.