Study of SCN Neurochemistry using in Vivo Microdialysis in the Conscious Brain: Correlation with Circadian Activity Rhythms.

In recent studies we demonstrated that pretreatment of hamsters with specific 5-HT receptor agonists, or the serotonin 5-HT precursor, tryptophan, markedly attenuated a variety of light-induced responses of the SCN clock, These included immediate-early gene Fos activation in SCN cells, light-mediated SCN field potentials, phase-shifts of the free-running circadian activity rhythm and phase advances of the light-entrained activity rhythm. Based upon these clear and repeatable effects of 5-HT in the SCN, it was hypothesized that 5-HT modulates the effect of light on the timing of circadian physiological and behavioral rhythms. The central findings of the funded studies were that endogenous 5-HT released from terminals within the SCN has physiological roles in 1 modulating the strength of the photic entraining signal relayed to the SCN from the retina and 2 eliciting phase-shifts in the activity of the circadian clock. These results point to a potentially powerful means of pharmacologically manipulating the human circadian system as a strategy for ameliorating circadian-related disfunctions.