Abstract

The retino-hypothalamic tract has been considered to be pre-eminent in linking the retina to the suprachiasmatic nucleus (SCN). Light detected by the retina results in release of excitatory amino acid transmitters at the SCN and resetting of the pineal melatonin rhythm. This explanation of light entrainment of melatonin and other rhythms may be overly simplistic. We have found that serotonin agonists active at the 5-HT2c receptor mimic the phase shifting effects of light on melatonin rhythms in rats in vivo. The most potent agonist (DOI; 0.1 mg/kg sc.) administered at CT18 resulted in an immediate transient suppression of melatonin production (assessed by the urinary excretion of 6-sulphatoxymelatonin) similar to that observed with a light pulse (2 lux/15 seconds). On subsequent nights the onset of metabolite excretion was delayed by 1.2 ± 0.2 hours. Further observations on the immunocytochemical localisation 5-HT2c receptors in the SCN and the induction of c-Fos in the SCN by 5-HT2c agonists strongly suggests that a serotonergic pathway is utilised for both light induced suppression and phase shifting of melatonin rhythms in the rat. These results open up the possibility of manipulating SCN and melatonin and other rhythms in humans with serotonergic drugs in situations where once light and/or melatonin were the only choices.