N-methyl-D-aspartate receptor complex modulation by neuropeptide Y and peptide YY in rat hippocampus in vitro

Neuropeptide Y (NPY) and peptide YY (PYY) are known to bind with high affinity to sigma (sigma) and phencyclidine (PCP) binding sites in rat brain. The functional significance of these results was assessed by testing both peptides in an in vitro bioassay system used for studying the N-methyl-D-aspartate (NMDA) receptor and consisting of rat hippocampal slices preloaded with [3H]noradrenaline (NA) and maintained under superfusion. The addition of NMDA in the superfusion medium induced an efflux of [3H]NA from the slices and the presence of NPY and PYY produced an enhancement of the stimulating effect. These results suggest that NPY and PYY could have a modulatory role at the NMDA receptor complex through an interaction with the sigma and/or PCP receptor.