Dissociation of the effects of neuropeptide Y on feeding and memory: evidence for pre- and postsynaptic mediation.

In mice not deprived of food, centrally administered neuropeptide Y (NPY) increases feeding and improves retention. In this study, we examined the effect of C-terminal NPY fragments on feeding and on memory retention. Mice were trained to avoid footshock in a T-maze. After training NPY, NPY fragments (20-36 and 26-36) or saline were administered intracerebroventricularly. Food consumption was measured during the first hour after training and memory retention was measured one week after training. NPY elicited a 544% increase in feeding compared to the saline control. Neither NPY fragment significantly increased feeding. Both NPY and NPY(20-36) improved retention compared to the saline-treated group. NPY(26-36) did not improve retention. NPY administered to well-trained mice results in amnesia. As a further test of the differential effect of NPY on memory processing and eating, we determined in well-trained mice whether administration of NPY and NPY(20-36) resulted in amnesia. Both NPY and NPY(20-36) resulted in amnesia, but only NPY stimulated feeding. These results are compatible with NPY effects on feeding being mediated through postsynaptic (Y1)NPY receptors and effects on memory retention being mediated through presynaptic (Y2)NPY receptors.