Monoamine depletion blocks triazolam-induced phase advances of the circadian clock in hamsters.
Monoamine depletion blocks triazolam-induced phase advances of the circadian clock in hamsters.
复制标题
单胺消耗会阻止三唑仑诱导的仓鼠生物钟相位提前。
DOI：
10.1016/0006-8993(94)91241-6
复制
发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Turek,FW
中科院分区：
文献类型：
--
作者：
Penev,PD;Zee,PC;Turek,FW
在活动开始前 6 小时 (CT6) 注射短效苯二氮卓类药物三唑仑 (Tz)，可使仓鼠的昼夜节律起搏器出现大幅相位提前。运动活动和/或觉醒状态的增加被认为对于 Tz 的作用至关重要，这表明中枢单胺能系统可能参与这一过程。本研究探讨了利血平诱导的单胺消耗对仓鼠 Tz 相移效应的影响。在持续黑暗的环境下连续监测 16 只雄性金仓鼠（14 周龄）的轮跑活动。建立稳定的自由昼夜节律后，一半动物接受利血平（2.5 mg/kg，皮下注射），另一半接受载体治疗。十天后，所有动物在 CT6 时接受 Tz 注射（10 mg/kg i.p.），并再监测 2 周的昼夜节律活动节律。另外 10 只动物被用来使用高压液相色谱法测定利血平对中心单胺水平的影响。利血平治疗后，尽管单胺明显减少，但运动活动的昼夜节律仍持续存在，幅度降低，自由奔跑时间更长。在 CT6 处注射三唑仑会导致对照组出现较大的相位提前 (93.1 ± 14.9)，而在 8 只利血平治疗动物中，有 7 只动物的相位提前明显减弱 (3.12 ± 17.7 分钟，P < 0.01)。我们的结果表明，单胺能系统对于 Tz 对仓鼠昼夜节律系统的相移作用至关重要。
Injections with the short-acting benzodiazepine, triazolam (Tz), 6 h before activity onset (CT6) produce large phase advances of the circadian pacemaker in hamsters. An increase in locomotor activity and/or the state of arousal is considered essential for the effects of Tz, suggesting the potential involvement of central monoaminergic systems in this process. The present study examines the effect of reserpine-induced monoamine depletion on the phase-shifting effects of Tz in hamsters. Wheel running activity of 16 male golden hamsters (14 weeks old) was continuously monitored in constant darkness. After a stable free-running circadian rhythm was established half of the animals received reserpine (2.5 mg/kg, s.c.) and the other half vehicle treatment. Ten days later all animals were given Tz injections (10 mg/kg i.p.) at CT6 and the circadian activity rhythm was monitored for 2 more weeks. An additional 10 animals were used to determine the effect of reserpine on the central monoamine levels using high pressure liquid chromatography. A circadian rhythm of locomotor activity with reduced amplitude and longer free-running period persisted after reserpine treatment, despite the significant monoamine depletion. Triazolam injections at CT6 induced large phase-advances (93.1 ± 14.9) in the control group that were markedly attenuated in 7 out of the 8 reserpine-treated animals (3.12 ± 17.7min, P < 0.01). Our results suggest that monoaminergic systems are essential for the phase-shifting effect of Tz upon the circadian system in hamsters.