Chronic exposure to melatonin receptor agonists does not alter their effects on suprachiasmatic nucleus neurons

Previous studies have demonstrated that melatonin and a novel melatonin receptor agonist, S20098 (N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide), regulate neuronal firing activity of photically responsive cells in the suprachiasmatic nucleus in vivo. In the present study, we used several different methods to investigate the effects of chronic daily treatment with melatonin, S20098 (1.0 mg/kg, s.c.) or control vehicle for 14 d on responsiveness of suprachiasmatic nucleus cells to these agonists. Both chronic and acute application of drugs were carried out during the day-night transition period. We confirmed that suprachiasmatic nucleus cells from control animals were most sensitive at this circadian phase. Chronic drug treatments did not alter sensitivity of photically responsive suprachiasmatic nucleus cells to S20098 or melatonin given intraperitoneally (i.p.) or iontophoretically in vivo. Suprachiasmatic nucleus cells studied in brain slice preparations also responded similarly to micropressure ejections of melatonin receptor agonists regardless of drug pretreatment. These results indicate that chronic melatonin receptor agonist pretreatment does not result in desensitization of suprachiasmatic nucleus neuronal responses to these agonists during the daily phase of maximum melatonin sensitivity.