The neuropeptide YY5 receptor mediates the blockade of "photic-like" NMDA-induced phase shifts in the golden hamster

Circadian or daily rhythms generated from the mammalian suprachiasmatic nuc lei (SCN) of the hypothalamus can be synchronized by light and nonphotic st imuli. Whereas glutamate mediates photic information, nonphotic information can in some cases be mediated by neuropeptide Y (NPY) or serotonin. NPY or serotonin can reduce the phase-resetting effect of light or glutamate; how ever, the mechanisms and level of interaction of these two kinds of stimuli are unknown. Here we investigate the effect of NPY on the NMDA-induced pha se shift of the hamster SCN circadian neural activity rhythm by means of si ngle-unit recording techniques. NMDA (10-100 muM) applied in the early subjective night induced phase delay s in the time of peak firing, whereas doses in the millimolar range disrupt ed firing patterns. The NMDA-induced phase delay was blocked by coapplicati on of NPY (0.02-200 muM). NPY Y1/Y5 and Y5 receptor agonists, but not the Y 2 receptor agonist, blocked the NMDA-induced phase delay in a similar manne r as NPY. The coapplication of a Y5 but not Y1 receptor antagonist eliminat ed NPY blockade of NMDA-induced phase delays, suggesting that the Y5 recept or is capable of mediating the inhibitory effect of NPY on photic responses . These results indicate that nonphotic and photic stimuli may interact at a level at or beyond NMDA receptor response and indicate that the Y5 recept or is involved in this interaction. Alteration of Y5 receptor function may therefore be expected to alter synchronization of circadian rhythms to ligh t.