Edgar D M, Miller J D, Prosser R A, Dean R R, Dement W C
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 97304.
J Biol Rhythms. 1993 Spring;8(1):17-31. doi: 10.1177/074873049300800102.
The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT1A receptor agonist 8-OH-DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (tau) following treatment (-0.28 hr; p < 0.002). tau shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor tau effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 microliters at 100 microM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in tau. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker.
视交叉上核（SCN）接收来自中缝正中核和中缝背核的初级传入纤维，但这些投射在昼夜节律计时中的作用尚不清楚。体外对视交叉上核的研究表明，喹哌嗪，一种一般的血清素（5-HT）受体激动剂，可在神经元活动的昼夜节律中产生昼夜时间依赖性的相位提前和相位延迟。本研究探讨喹哌嗪和选择性5-HT1A受体激动剂8-OH-DPAT在体内是否同样有效。在昼夜时间（CT）6或CT 18皮下注射喹哌嗪（5-10mg/kg）前后，监测单独饲养在持续黑暗中的雄性Wistar大鼠的饮水和轮转运动模式，有无轮转运动轮。在CT 6时产生剂量依赖性的相位提前（20-180分钟）。在CT 18时未观察到明显的相移。CT 6喹哌嗪处理的动物在处理后也显示出节律周期（tau）持续且显著缩短（-0.28小时；p<0.002）。在CT 18喹哌嗪处理的大鼠中不一致地观察到tau缩短。喹哌嗪诱导的相移和tau效应均不依赖于轮转运动本身。通过脑室内注射将8-OH-DPAT注入第三脑室（在盐水中100 microM时为5微升）在CT 6时产生稍小的相位提前（20-90分钟），但在CT 18时未产生相位延迟或tau变化。这些发现支持了体外证据，即5-羟色胺能激动剂可使昼夜节律起搏器发生相移。
