Neuropeptide Y in the mammalian circadian system: effects on light-induced circadian responses

The present review examine the role of neuropeptide (NPY) in the circadian system, focusing on the interactions between light and NPY, especially during the subjective night. NPY has two different effects on the circadian system of mammals. On one hand, NPY, similar to behavioral stimulation, can change the phase of the clock by itself during the subjective day. On the other hand, NPY, again similar to behavioral stimulation, can inhibit the phase-shifting effect of light during the night. These effects of NPY may occur through different receptor subtypes, the Y2 receptor mediating day-time effects and the Y5 receptor mediating night-time effects of NPY. Our results also indicate that there are differences between in vivo and in vitro studies: NPY inhibition of in vivo light-induced phase shifts was observed only late in the subjective night; however, NPY applied in vitro could block light-induced phase shifts early in the subjective night as well. Contrasting these in vivo and in vitro results led us to suggest that the time of day of maximal effect of NPY in the intact animal may be a time when exogenous administration of NPY has little effect, due to saturation of the system. This situation could be an example of how the measurable output of the clock can be affected by the behavioral state in a different way at different time points, depending not only on the clock itself but also on behavior. If verified in human beings, the ability of NPY to modulate the circadian-clock responses to light may be of clinical importance.