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
• 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/2578714
• 关键词: antidepressants; body temperature regulation; brain regulatory center; chlorpromazine; circadian rhythms; dorsal raphe nucleus; electroencephalography; haloperidol; hamsters; hypothalamus; photostimulus; psychomotor function; psychopharmacology; serotonin; sleep; vasoactive intestinal peptide

The therapeutic mechanism of antidepressant drugs is likely to include a circadian component. This possibly is being examined by testing in hamsters the effects of antidepressant and neuroleptic drugs on the sate of the circadian pacemaker that controls daily rhythms of motor activity, temperature and EEG sleep. Different classes of psychoactive drugs differentially alter the circadian pattern of temperature within the hypothalamus, the brain region containing the circadian pacemaker as well as central thermostat which regulates body temperature. Chronic antidepressant drug treatments decrease hypothalamic temperature during the rest (light) phase. The neuroleptic drugs (chlorpromazine and haloperidol) increases hypothalamic temperature during the rest phase. Antidepressant drugs and neuroleptic drugs increase and decrease respectively, the circadian amplitude of hypothalamic temperature. In depressed patients, elevated body temperature is often observed during nocturnal rest. Pharmacological and non-pharmacological treatments of depression have been reported to lower body temperature. We hypothesize that decreased hypothalamic temperature, particularly during the nocturnal rest phase, is an important component of the therapeutic response to pharmacological and non-pharmacological treatments for depression. A recent line of investigation has explored the role of serotonin in modulating the circadian system response to light. VIP cells within the SCN are of interest for two reasons. First, the visual pathway for circadian entrainment, and a serotonergic pathway originating in the raphe nucleus, both project of these VIP cells. Second, VIP levels within the SCN exhibit seasonal variation as a result of changes in daylength. VIP cells may therefore be part of a seasonal mechanism that controls circadian variation in light responsiveness and behavior. The relationship between vasoactive intestinal peptide (VIP) containing cells, and serotonin levels within the suprachiasmatic nucleus (SCN) is being examined using immunohistochemical and image analysis techniques. We have found that chronic treatment with the antidepressant drug clorgyline elevates immunoreactivity to vasoactive intestinal peptide (VIP) throughout the rostral caudal extent of the SCN. This is the first description of a chronic antidepressant drug affecting VIP within the SCN. The increase in VIP immunoreactivity is likely to be related to chronic elevation of serotonin within the SCN since serotonergic fibers project to VIP cells within the SCN. It is hypothesized that in seasonal depression, the behavioral effect on circadian rhythms (e.g. sleep- wakefulness) of serotonergic antidepressant drugs, is mediated by the drug effect on VIP cells within the SCN.

抗抑郁药物的治疗机制可能包括 昼夜节律成分。这可能正在通过测试进行检验， 抗抑郁和抗精神病药物对仓鼠状态的影响 昼夜节律起搏器控制运动活动的日常节奏， 体温和脑电图睡眠。 不同种类的精神活性药物不同程度地改变 下丘脑和大脑的昼夜节律 包含昼夜节律起搏器和中央恒温器的区域 调节体温慢性抗抑郁药物治疗 在休息（光）阶段降低下丘脑温度。的 抗精神病药物（氯丙嗪和氟哌啶醇）增加下丘脑 休息阶段的温度。抗抑郁药和神经安定药 药物分别增加和减少， 下丘脑温度在抑郁症患者中， 夜间休息时经常观察体温。药理学和 据报道，抑郁症的非药物治疗可以降低 体温我们假设下丘脑温度下降， 尤其是在夜间休息阶段， 对药物和非药物的治疗反应 抑郁症的治疗 最近的一项研究探索了血清素在 调节昼夜节律系统对光的反应。VIP细胞内 SCN的兴趣有两个原因。第一，视觉路径 昼夜节律的夹带，和一个β-肾上腺素能途径起源于 中缝核，都是这些VIP细胞的投射。第二，内部VIP级别 SCN由于日照长度变化而表现出季节性变化。 因此VIP细胞可能是季节性机制的一部分， 光反应和行为的昼夜变化。的 血管活性肠肽（VIP） 视交叉上核（SCN）内的5-羟色胺水平 使用免疫组织化学和图像分析技术进行检查。 我们发现长期服用抗抑郁药物 氯吉林增强血管活性肠肽免疫反应性 (VIP)贯穿SCN的喙尾侧范围。这是第一 描述了一种影响VIP的慢性抗抑郁药， SCN。VIP免疫反应性的增加可能与 SCN内5-羟色胺的慢性升高， 投射到SCN内的VIP小区。据推测，在季节性 抑郁症，对昼夜节律的行为影响（例如睡眠- 觉醒），是介导的 药物对SCN内VIP细胞的作用。