Entrainment of rat circadian rhythms by melatonin does not depend on the serotonergic afferents to the suprachiasmatic nuclei.

Daily administration of melatonin (MEL) can entrain rat circadian rhythms free-running in constant darkness. The high MEL doses needed to obtain entrainment suggest the implication of other neural mechanisms than simply an effect on the hormone's specific receptors detected in the SCN. Administration of serotonin receptor agonists can phase-shift the rodent circadian clock, and MEL is known to modulate release and reuptake of serotonin in nerve endings. This raises the question of a critical involvement of 5-HT-fibres in the entraining properties of MEL. The aim of the present study was to test this hypothesis. Bilateral neurotoxic (5,7-dihydroxytryptamine) lesions of the serotonergic fibres in the SCN were performed in animals kept in LD 12:12. Following the post-operative period, the animals were transferred to constant darkness to free-run. MEL was then administered by a 1 h daily infusion. Both well lesioned and intact animals entrained to MEL. No differences were observed between lesioned and control animals on parameters such as the phase-angles between MEL onset and activity onset, and core body temperature acrophase, respectively. Entrainment of rat circadian rhythms to exogenous MEL is thus not directly dependent on the 5-HT fibres in the SCN.