Cutrera R A, Kalsbeek A, Pévet P
Neurobiologie des Fonctions Rythmiques et Saisonnières URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
Behav Brain Res. 1994 May 30;62(1):21-8. doi: 10.1016/0166-4328(94)90034-5.
Administration of Triazolam (Tz)--a short acting benzodiazepine (BZ)--induces permanent phase-shifts in locomotor activity of golden hamsters (Mesocricetus auratus). However, the target area(s) as well as the mechanism involved in the Tz-induced changes are not known. Previous results indicated that raphe nuclei (RN) would appear to be a likely site for Tz-induced phase shifts. Therefore, we specifically destroyed the 5-HT fibers connecting the RN with the SCN--the site of the endogenous mammalian clock--by microinjections of the selective neurotoxin 5,7 dihydroxytryptamine (5,7-DHT) at the level of SCN. Infusion of 5,7-DHT resulted in long lasting damage of the ascending serotonergic projection from RN to the hypothalamus. Subsequently, the phase-shifting effect of Tz was investigated. Only complete or almost complete depletion of the 5-HT input to the SCN was accompanied with a pronounced reduction of the phase shift together with a significant reduction of wheel-running activity during the 6 h following Tz injection. Our present results support the view that the 5-HT innervation of the SCN represents an essential link in the phase-shifting action following peripheral Tz injections.
给予三唑仑（Tz）——一种短效苯二氮䓬类药物（BZ）——会使金黄地鼠（Mesocricetus auratus）的运动活动出现永久性相位偏移。然而，Tz诱导变化所涉及的靶区域以及机制尚不清楚。先前的结果表明，中缝核（RN）似乎是Tz诱导相位偏移的一个可能部位。因此，我们通过在视交叉上核（SCN）水平微量注射选择性神经毒素5,7-二羟色胺（5,7-DHT），特异性地破坏了连接RN与SCN（内源性哺乳动物生物钟所在部位）的5-羟色胺能纤维。注入5,7-DHT导致从RN到下丘脑的上行5-羟色胺能投射受到持久损伤。随后，研究了Tz的相位偏移效应。只有向SCN的5-羟色胺能输入完全或几乎完全耗尽，才会伴随着相位偏移的显著减少以及在注射Tz后的6小时内轮转活动的显著降低。我们目前的结果支持这样一种观点，即SCN的5-羟色胺能神经支配是外周注射Tz后相位偏移作用中的一个重要环节。
