Does neuropeptide Y contribute to the modulation of brain stimulation reward by chronic food restriction?

The rewarding effect produced by electrically stimulating particular sites in the lateral hypothalamus (LH) can be enhanced by chronic food restriction and body weight loss. The impact on brain stimulation reward (BSR) of certain hormones involved in the regulation of energy balance, such as leptin and corticotropin-releasing hormone, depends upon the sensitivity of BSR to food restriction. The present investigation assessed the influence of neuropeptide Y (NPY), a potent orexigenic peptide, on BSR generated by stimulating restriction-sensitive and -insensitive sites in the LH. Twelve male Long Evans rats were trained to press a lever for a rewarding train of stimulation. Rate-frequency curves, reflecting the number of rewards earned as a function of the stimulation frequency, were collected during free-feeding and then again following a period of food restriction and 20-25% body weight loss. NPY (4 microg) was administered intraventriculary during the food restriction condition. Alterations in the rewarding effect of the stimulation were assessed by measuring changes in the frequency required to maintain half-maximal rewards earned (M-50). In half of the subjects, food restriction produced significant decreases in M-50 values, indicating that the reward effectiveness of the stimulation was potentiated. In contrast, M-50 values were unaltered by food restriction in the remaining six animals. In most of the subjects in which M-50 values decreased following chronic food restriction, NPY failed to alter BSR. Similarly, BSR was unchanged by NPY administration in most of the rats with restriction-insensitive stimulation sites. These findings suggest that NPY does not take part in the process whereby food restriction and leptin modulate reward circuitry activated by stimulating restriction-sensitive sites.