The neuropeptide Y Y5 receptor mediates the blockade of "photic-like" NMDA-induced phase shifts in the golden hamster

Abstract

Circadian or daily rhythms generated from the mammalian suprachiasmatic nuclei (SCN) of the hypothalamus can be synchronized by light and nonphotic stimuli. 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; however, 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 phase shift of the hamster SCN circadian neural activity rhythm by means of single-unit recording techniques. NMDA (10-100 μM) applied in the early subjective night induced phase delays in the time of peak firing, whereas doses in the millimolar range disrupted firing patterns. The NMDA-induced phase delay was blocked by coapplication of NPY (0.02-200 μM). NPY Y1/Y5 and Y5 receptor agonists, but not the Y2 receptor agonist, blocked the NMDA-induced phase delay in a similar manner as NPY. The coapplication of a Y5 but not Y1 receptor antagonist eliminated NPY blockade of NMDA-induced phase delays, suggesting that the Y5 receptor 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 receptor is involved in this interaction. Alteration of Y5 receptor function may therefore be expected to alter synchronization of circadian rhythms to light.