Inhibitory action of brotizolam on circadian and light‐induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus
Inhibitory action of brotizolam on circadian and light‐induced Per1 and Per2 expression in the hamster suprachiasmatic nucleus
复制标题
溴替唑仑对昼夜节律和光诱导的仓鼠视交叉上核 Per1 和 Per2 表达的抑制作用
DOI：
10.1038/sj.bjp.0703735
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发表时间：
2000
影响因子：
7.3
通讯作者：
S. Shibata
中科院分区：
文献类型：
--
作者：
Shin;K. Horikawa;M. Akiyama;T. Moriya;S. Ebihara;Goyo Komuro;Tatsuro Ohta;S. Shibata
据报告，在主观日间注射后，三唑仑导致仓鼠轮跑节律的相位提前。然而，目前尚不清楚苯二氮卓类药物是否会影响Per基因的表达，伴随着行为相移。当在中间主观日间（昼夜节律时间6或9）注射溴替唑仑（0.5-10 mg kg−1）时，诱导仓鼠节律的大相位提前，但在昼夜节律时间0、3或15时不诱导。 溴替唑仑（5 mg kg−1）在昼夜节律时间6注射后1和2 h显著降低了视交叉上核中Per 1和Per 2的表达，并在昼夜节律时间20略微降低。 在主观白天注射8-OH-DPAT（5 mg kg-1）诱导了类似的相位提前，Per 1和Per 2表达减少。 溴替唑仑与8-OH DPAT联合给药未能增强8-OH DPAT诱导的相位提前，并降低Per表达。与溴替唑仑5 mg kg−1共同处理后，在昼夜节律时间20光照（5 lux，15 min）后，交叉上核中Per 1和Per 2的相位提前和快速诱导均强烈减弱。 本研究结果强烈表明，减少Per 1和/或Per 2的表达在主观白天溴替唑仑可能是一个重要的步骤，导致行为相提前。联合给药实验表明，共同机制涉及溴替唑仑或8-OH DPAT诱导的相位提前和Per基因表达降低。这些结果表明，溴替唑仑不仅是一种治疗失眠的好药物，而且是一种能够像褪黑激素一样促进再夹带的药物。
Triazolam reportedly causes phase advances in hamster wheel‐running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the Per gene expression accompanying a behavioural phase shift. Brotizolam (0.5–10 mg kg−1) induced large phase advances in hamster rhythm when injected during mid‐subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg−1) significantly reduced the expression of Per1 and Per2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8‐OH‐DPAT (5 mg kg−1) at subjective daytime induced similar phase advances with a reduction of Per1 and Per2 expression. Co‐administration of brotizolam with 8‐OH DPAT failed to potentiate the 8‐OH DPAT‐induced phase advances and reduced Per expression. Both phase advance and rapid induction of Per1 and Per2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co‐treatment with brotizolam 5 mg kg−1. The present results strongly suggest that reduction of Per1 and/or Per2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co‐administration experiment suggests that common mechanism(s) are involved in brotizolam‐ or 8‐OH DPAT‐induced phase advances and the reduction of Per gene expression. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re‐entrainment like melatonin.