The present experiments were undertaken to explore a role for serotonin (5-HT) in modulating photic signal transduction and extracellular glutamate (Glu) concentration in the suprachiasmatic nuclei (SCN) of the Syrian hamster. Pretreatment with an i.p. injection of the serotonergic, quipazine, caused a marked decrease in the number of SCN cells expressing Fos protein-like immunoreactivity (Fos-LI) induced by a light pulse delivered during the latter part of the dark phase (7 h after lights-off; 55.6 +/- 7.5% of vehicle controls, P < 0.004). This effect of quipazine was dose-dependent and was limited principally to the ventrolateral region of the SCN. In a likewise manner, intra-SCN microinjection of quipazine inhibited light-induced Fos-LI in the ventrolateral SCN, indicating that the suppressive action of quipazine is centered in the SCN. In a separate experiment, localized perfusion of the SCN region with 5-HT using the microdialysis technique caused a significant reduction in the extracellular concentration of Glu. The effect was greater during the dark phase, compared to the light phase of the day-night cycle (60.7 +/- 6.8% vs. 39.3 +/- 6.8% maximal suppression, respectively; P < 0.05). Similar localized application of quipazine also decreased extracellular Glu (48.0 +/- 6.1% maximal suppression; P < 0.05). Collectively, these results are evidence for a serotonergic modulation of retinohypothalamic input in the SCN, which could involve a presynaptic inhibition of Glu release.