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

Abstract

Both excitatory amino acids and serotonin have been implicated in the photic control of rhythms, but they have rarely been considered to interact. This 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 serotonin agonist DOI ((+/-)-1-(4-Iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride). 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 group. 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 nights. Pre-treatment with MK-801 also inhibited by approximately 90% the induction of c-fos 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-HT(2C) agonists in the rat.