Specific destruction of the serotonergic afferents to the suprachiasmatic nuclei prevents triazolam-induced phase advances of hamster activity rhythms.
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.
Cutrera
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Neurobiologie des Fonctions Rythmiques et Saisonnières URA-CNRS 1332, Université Louis Pasteur, Strasbourg, France.
Kalsbeek
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Pévet
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D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000204:Activity Cycles / Q000187:drug effects*; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001931:Brain Mapping; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects*; D009412:Nerve Fibers / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects*; D014229:Triazolam / Q000494:pharmacology*
D011985:Receptors, Serotonin; D014229:Triazolam; D015116:5,7-Dihydroxytryptamine