Neuropeptide Y blocks GABAB-induced phase-shifts of the suprachiasmatic circadian clock in vitro.

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) generates 24-h rhythms of neuronal activity in vitro. We have previously shown that the GABAB agonist baclofen resets the SCN pacemaker in vitro in a phase-dependent manner: advances are induced at zeitgeber time (ZT) 6 and delays are induced at ZT 22. We have also previously shown that neuropeptide Y (NPY) phase-shifts the SCN clock when applied at ZT 10 but not at other times. Here, we show that NPY blocks the baclofen-induced phase-shifts at ZT 6 and ZT 22. The inhibition by NPY appears dose-dependent, and a higher concentration of NPY is required for complete inhibition of the baclofen-induced phase-advances than the phase-delays. Conversely, NPY-induced phase-shifts at ZT 10 are unaffected by co-application of baclofen. These results are consistent with previous findings showing that NPY blocks in vitro phase-shifts induced by a variety of neuromodulators during both the daytime and nighttime.