Melatonin inhibits in vitro serotonergic phase shifts of the suprachiasmatic circadian clock

The suprachiasmatic (SCN) circadian pacemaker generates 24 h rhythms of spo ntaneous neuronal activity when isolated in an acute brain slice preparatio n. The isolated pacemaker also retains its capacity to be reset, or phase-s hifted by exogenous stimuli. For example, serotonin (5-HT) agonists advance the SCN pacemaker when applied during mid subjective day, while neuropepti de Y (Npy) agonists and melatonin advance the pacemaker when applied during late subjective day. Previous work has demonstrated interactions between N PY and 5-HT agonists, such that NPY can block 5-HTergic phase advances, whi le 5-HT agonists do not prevent NPY-induced advances. Due to a number of si milarities in the actions of melatonin and NPY in the SCN, it seemed possib le that melatonin and 5-HT might interact in the SCN as well. Therefore, in this study potential interactions between melatonin and 5-HT agonists were explored. Melatonin inhibited phase advances by the 5-HT agonist, (+)DPAT, and this inhibition was decreased by co-application of tetrodotoxin. Conve rsely, melatonin was unable to block phase advances by the cyclic AMP analo g, 8BA-cAMP. Finally, neither 5-HT agonists nor 8BA-AMP were able to block melatonin-induced phase advances. These results demonstrate a clear interac tion between melatonin and 5-HT in the SCN, and suggest that melatonin and NPY may play similar roles with respect to modulating the phase of the SCN circadian pacemaker in rats. (C) 1999 Elsevier Science B.V. All rights rese rved.