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Tryptophan Loading Modulates Light-Induced Responses in the Mammalian Circadian System

Department of Biological Sciences, Kent State University, Kent, OH 44242

M. Selim

Department of Biological Sciences, Kent State University, Kent, OH 44242

G. Srkalovic

Department of Biological Sciences, Kent State University, Kent, OH 44242

M.A. Rea

Biological Rhythms and Integrative Neuroscience Research Institute, Armstrong Laboratory, Brooks AFB, TX 78235

Enhanced endogenous serotonergic activity, stimulated by L-tryptophan (TRYPT) loading, was found to have a substantial impact on neurochemical and behavioral aspects of the circadian response to light in the male Syrian hamster. An intraperitoneal (i.p.) injection of 150 mg/kg TRYPT significantly stimulated serotonin (5-HT) release in the suprachiasmatic nuclear (SCN) region, as reflected by a 205 ± 30% maximal increase in the extracellular concentration of 5-HT assessed using microdialysis. Administration of TRYPT 1 h before exposure to a light pulse (30 min, 40 lux) delivered during late subjective night dose-dependently suppressed the number of SCN cells expressing light-induced Fos-like immunoreactivity (Fos-LI; maximal suppression @200 mg/kg was 77 ± 4%, p < 0.001). This action of TRYPT was attenuated by pretreatment with the 5-HT_1a antagonist, NAN-190, and was abolished by the 5-HT₂/5-HT₇ antagonist, ritanserin, or the nonselective 5-HT antagonist, metergoline (all 10 mg/kg). These antagonists alone had no effect on light-induced Fos. In a second experiment, pretreatment of free-running hamsters 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 19) significantly attenuated the light-induced phase advances of the circadian activity rhythm (66 ± 7 min vs. 100 ± 6 min for vehicle controls; 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 the 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 extracellular concentration of glutamate in the SCN region assessed using microdialysis (55 ± 8% suppression; p < 0.05 vs. baseline). These results support the hypothesis that the ascending serotonergic projection to the SCN modulates photic entrainment processes within the circadian oscillator.

Key Words: SCN • tryptophan • serotonin • retinohypothalamic tract • Fos • behavior • circadian rhythm • Syrian hamster

Journal of Biological Rhythms, Vol. 10, No. 1, 80-90 (1995)
DOI: 10.1177/074873049501000107


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