Ozaki N, Duncan W C, Johnson K A, Wehr T A
Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res. 1993 Nov 5;627(1):41-8. doi: 10.1016/0006-8993(93)90746-a.
In Syrian hamsters, chronic administration of the type A monoamine oxidase inhibitor, clorgyline (CLG), alters the intrinsic period and daily pattern of the circadian rhythm of wheel running, and changes the intensity-response curve for phase-shifting of the rhythm by light pulses. Chronic treatment with CLG also decreases hypothalamic and peritoneal temperatures, particularly during the rest phase of the activity-rest cycle. To help identify monoamines that may mediate CLG's effects on circadian rhythms, we measured levels of dopamine (DA) and serotonin (5-HT) at nine time points over a 24-h period in micro-dissected brain regions in chronic CLG-treated or saline-treated hamsters. For 5-HT, a diurnal variation was detected in all regions in saline-treated animals; for DA, no diurnal variation was detected in any region. In all regions, 5-HT levels and, to a lesser extent, DA levels were higher after CLG treatment. The acrophase of the 5-HT rhythm in the suprachiasmatic nucleus (SCN) was delayed by CLG-treatment, while the acrophase in the dorsal raphe nucleus was unchanged. The diurnal variation of 5-HT in the paraventricular nucleus of the hypothalamus, medial preoptic area, and median raphe nuclei was no longer detectable after chronic CLG-treatment. The phase-delay induced by CLG treatment in the daily rhythm of serotonin levels in the SCN, which functions as a circadian pacemaker, may be an important mechanism underlying the drug's capacity to slow the intrinsic rhythm of the pacemaker and to phase-delay behavioral rhythms that are under its control.
在叙利亚仓鼠中，长期给予A型单胺氧化酶抑制剂氯吉兰（CLG）会改变转轮行为昼夜节律的固有周期和日模式，并改变光脉冲对节律进行相位转移的强度-反应曲线。CLG的长期治疗还会降低下丘脑和腹膜温度，尤其是在活动-休息周期的休息阶段。为了帮助确定可能介导CLG对昼夜节律影响的单胺类物质，我们在慢性CLG处理或生理盐水处理的仓鼠的显微解剖脑区中，在24小时内的九个时间点测量了多巴胺（DA）和5-羟色胺（5-HT）的水平。对于5-HT，在生理盐水处理的动物的所有脑区中均检测到昼夜变化；对于DA，在任何脑区均未检测到昼夜变化。在所有脑区中，CLG处理后5-HT水平升高，DA水平也有所升高，但升高幅度较小。CLG处理使视交叉上核（SCN）中5-HT节律的峰值相位延迟，而中缝背核中的峰值相位未改变。慢性CLG处理后，下丘脑室旁核、内侧视前区和中缝正中核中5-HT的昼夜变化不再能被检测到。CLG处理诱导SCN中血清素水平的日常节律出现相位延迟，而SCN作为昼夜起搏器，这可能是该药物减缓起搏器固有节律并使受其控制的行为节律出现相位延迟能力的重要机制。
