MK-801 administration blocks the effects of a 5-HT2A/2C agonist on melatonin rhythmicity and c-fos induction in the suprachiasmatic nucleus

Both excitatory amino acids and serotonin have been implicated in the photi c control of rhythms, but they have rarely been considered to interact. Thi s study investigated the effects of the NMDA receptor antagonist, MK-801 on the phase shift of the melatonin rhythm and the induction of c-fos in the rat suprachiasmatic nucleus (SCN) provoked by the administration of the ser otonin agonist DOI ((+/-)-1-(4-Iodo-2,5-dimethoxyphenyl)-2-aminopropane hyd rochloride). The urinary excretion rate rhythm of the melatonin metabolite, 6-sulphatoxymelatonin was delayed by administration of DOI (0.5 mg/kg) at CT18 (6 h after subjective darkness onset) as previously reported by our gr oup. Administration of MK-801 (3 mg/kg) 30 min before DOI blocked the shift in the onset of excretion of the melatonin metabolite on the following nig hts. Pre-treatment with MK-801 also inhibited by approximately 90% the indu ction of c-fas in the SCN by DOI at ZT18 (6 h after actual darkness onset) as determined by immunohistochemistry. These results provide evidence for a role of excitatory amino acids in the photomimetic effects of serotonin 5- HT2C agonists in the rat. (C) 1999 Elsevier Science B.V. All rights reserve d.