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.