Characterization of melatonin-induced fos-like immunoreactivity in the hypothalamic suprachiasmatic nucleus of the rat

The hypothalamic suprachiasmatic nucleus (SCN) is primarily responsible for the regulation of circadian rhythmicity. Melatonin, the pineal-derived neu rohormone, modulates the rhythmic output of the SCN. Properly timed exposur e to melatonin is able to induce changes in rhythmic function and thereby e ntrain circadian rhythms of activity. c-fos is an immediate early gene that is transiently expressed in neurons i n response to receptor activation. The ventrolateral portion of the SCN (vS CN) is activated in response to phase-shifting stimuli, an event which is m arked by an increase in the expression of c-fos. In the present study, rats systemically administered the melatonin agonist 2-iodomelatonin at CT 22 demonstrated significant dose-dependent Fos immuno reactivity within the vSCN, an effect which was significantly inhibited by the melatonin antagonist N-acetyltryptamine. The Fos expression observed in the vSCN was not affected by treatment with the serotonin antagonist ketan serin or the alpha-adrenergic antagonist phentolamine. Moreover, antisense oligonucleotides to c-fos, significantly blocked the ability of 2-iodomelat onin to induce Fos expression in the vSCN at CT 22. These results pharmacologically characterize melatonin-induced c-fos expres sion in the rat vSCN and provide evidence to support a c-fos-mediated mecha nism through which the activation of melatonin receptors may be linked to t he long-term molecular regulation of circadian rhythms controlled by the SC N.