TRYPTOPHAN LOADING MODULATES LIGHT-INDUCED RESPONSES IN THE MAMMALIANCIRCADIAN SYSTEM

Enhanced endogenous serotonergic activity, stimulated by L-tryptophan (TRYPT) loading, was found to have a substantial impact on neurochemic al and behavioral aspects of the circadian response to Light in the ma le Syrian hamster. An intraperitoneal (i.p.) injection of 150 mg/kg TR YPT significantly stimulated serotonin (5-HT) release in the suprachia smatic nuclear (SCN) region, as reflected by a 205 +/- 30% maximal inc rease in the extracellular concentration of 5-HT assessed using microd ialysis. Administration of TRYPT 1 h before exposure to a light pulse (30 min, 40 lux) delivered during late subjective night dose-dependent ly suppressed the number of SCN cells expressing light-induced Fos-lik e immunoreactivity (Fos-LI; maximal suppression @200 mg/kg was 77 +/- 4%, p < 0.001). This action of TRYPT was attenuated by pretreatment wi th the 5-HT1a antagonist, NAN-190, and was abolished by the 5-HT2/5-HT 7 antagonist, ritanserin, or the nonselective 5-HT antagonist, metergo line (all 10 mg/kg). These antagonists alone had no effect on light-in duced Fos. In a second experiment, pretreatment of free-running hamste rs housed under constant darkness with 150 mg/kg TRYPT 45-60 min prior to light exposure (10 min, 20 lux) during late subjective night (CT 1 9) significantly attenuated the Light-induced phase advances of the ci rcadian activity rhythm (66 +/- 7 min vs. 100 +/- 6 min for vehicle co ntrols; p < 0.001). The same dose of TRYPT given 1 h before Lights-on for 5 consecutive days in hamsters maintained under 14L:10D altered th e phase angle of entrainment such that activity onsets were delayed by 36 +/- 8 min relative to controls (p < 0.05). The same dose of TRYPT administered during late subjective night also suppressed the extracel lular concentration of glutamate in the SCN region assessed using micr odialysis (55 +/- 8% suppression; p < 0.05 vs. baseline). These result s support the hypothesis that the ascending serotonergic projection to the SCN modulates photic entrainment processes within the circadian o scillator.