Schuhler S, Saboureau M, Pitrosky B, Pévet P
CNRS-UMR 7518, Laboratoire de Neurobiologie des Fonctions Rythmiques et Saisonnières, Université Louis Pasteur, Strasbourg, France.
Neurosci Lett. 1998 Oct 30;256(1):33-6. doi: 10.1016/s0304-3940(98)00749-6.
8-Hydroxy-2-[di-n-propylamino]-tetralin) (8-OH-DPAT), a 5-HT1A/7 receptor agonist, has a chronobiological effect on the circadian system. To identify how the 8-OH-DPAT exerts this effect, we specifically destroyed the serotonergic (5-HT) fibres connecting the median raphe nuclei (RN) to the suprachiasmatic nuclei (SCN) of the hypothalamus by using microinjections of a neurotoxin 5,7-dihydroxytryptamine into the SCN. After administration of 8-OH-DPAT (0.1 ml, 5 mg/kg) at circadian time 7, the control and the 'partially-lesioned' animals showed a large phase-advance whereas in the 'well-lesioned' hamsters the phase-advances were significantly reduced or absent. The present study demonstrates that, in the Syrian hamster, the 5-HT fibres connecting the RN to the SCN are essential for the phase-shifting action of peripheral 8-OH-DPAT injections, and that the drug does very probably not exert its chronobiological effect directly onto SCN neurons but through receptors localized on median raphe nucleus neurons.
8-羟基-2-[二正丙基氨基]四氢萘(8-OH-DPAT)是一种5-HT1A/7受体激动剂,对昼夜节律系统具有生物钟效应。为了确定8-OH-DPAT如何发挥这种效应,我们通过向视交叉上核(SCN)微量注射神经毒素5,7-二羟基色胺,特异性地破坏了连接中缝核(RN)与下丘脑视交叉上核(SCN)的5-羟色胺能(5-HT)纤维。在昼夜时间7给予8-OH-DPAT(0.1毫升,5毫克/千克)后,对照动物和“部分损伤”动物出现了大幅的相位提前,而在“严重损伤”的仓鼠中,相位提前显著减少或未出现。本研究表明,在叙利亚仓鼠中,连接RN与SCN的5-HT纤维对于外周注射8-OH-DPAT的相位移动作用至关重要,并且该药物很可能不是直接作用于SCN神经元来发挥其生物钟效应,而是通过位于中缝核神经元上的受体来实现。