LOCAL-ADMINISTRATION OF SEROTONIN AGONISTS BLOCKS LIGHT-INDUCED PHASEADVANCES OF THE CIRCADIAN ACTIVITY RHYTHM IN THE HAMSTER

Circadian rhythms in mammals are synchronized to environmental light-d ark cycles through a direct retinal projection to the suprachiasmatic nucleus (SCN), a circadian clock. This process is thought to be modula ted by other afferents to the SCN, including a dense serotonergic proj ection from the midbrain raphe. Previous work from this laboratory dem onstrated that a systemically administered 5-hydroxyhyptamine(1A/7) (5 -HT1A/7) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) do se dependently attenuates Light-induced phase shifts of the circadian activity rhythm of the Syrian hamster. In this study, we demonstrate t hat local injections (1-100 mu M) of the 5-HT1A/7 agonists 8-OH-DPAT o r 5-carboxamidotryptamine into the region of the SCN inhibit light-ind uced phase advances of the circadian wheel-running rhythm. In addition , the inhibitory effects of systemically administered 8-OH-DPAT were u naffected by either radiofrequency-induced lesions of the intergenicul ate leaflet or 5,7-dihydroxytryptamine-induced lesions of serotonergic projections to the SCN. These findings support a modulatory role of s erotonin in photic regulation of circadian phase through an action at the level of the SCN.