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
• 负责人: W C DUNCAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3845266
• 关键词: MAO inhibitors; antidepressants; biological clocks; bioperiodicity; body temperature regulation; circadian rhythms; drug metabolism; glutamates; hamsters; lithium; neurophysiology; photobiology; photostimulus; phototherapy; seasons; sleep disorders; suprachiasmatic nucleus; visible light; visual photosensitivity; visual phototransduction; visual threshold

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.

在这个项目中，我们研究了神经系统的生理特性， 介导光对每日和夜间时间的影响的途径， 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 战斗会重置生物钟的时间和行为模式 由时钟控制。 本研究主要有两个方面。 第一、 我们研究了光脉冲的时钟相位重置特性， 不同的强度和持续时间在无药物的动物。 二是 研究慢性抗抑郁药物治疗对生物钟的影响 光的相位重置特性。 有三个主要的发现， 最近的调查 首先，我们证实了在无药物的仓鼠中， 该途径在整个昼夜循环中是恒定的。 也就是说， 在不同的昼夜节律阶段传递的等量光 在每个相位产生最大响应的50%的相移。 第二，这些实验表明， 抗抑郁药氯吉兰降低了对光线的敏感性， 这种效应的大小取决于昼夜节律的相位 光传递的周期。 因此，需要更多的光来 产生一个50%的相移响应晚上光比产生一个50%的 对晨光的反应。 敏感性的日常模式的转变 可能有助于这种药物的抗抑郁特性。 目前正在研究这种敏感性变化的机制。 这种药物可能会随着时间的推移改变光的整合。 第三，尽管先前发表的报告表明，锂改变了 通过眼电图测量的视觉反应， 神经生理学技术，我们最近的数据表明， 不能改变光的敏感性或响应性， 夹带途径 这些结果强调了这样一种观点，即这种光 系统，这是负责夹带昼夜节律，是 与其他视觉系统分开。 例如，光系统 介导夹带具有高响应阈值（约6个对数单位 高于视觉阈值），并将光刺激整合达45 分钟（与某些视杆光感受器的1 - 3秒相反）。 的 事实上，锂改变视觉反应，但不是夹带反应 光强调有必要对此进行进一步的研究 特殊和独特的光系统。