Different brain loci mediate neuropeptide Y's effects on feeding vs. reward

grantor: University of TorontoThere is a high co-prevalence of eating disorders mid substance abuse in humans. One theory offered to account for this relationship implicates a common biochemical substrate in the pathophysiology of both disorders. Neuropeptide Y (NPY), a 36 amino-acid peptide found throughout neurons of the central and peripheral nervous systems, may be one candidate serving both roles. NPY stimulates voracious feeding in previously satiated rats when injected into the perifornical hypothalamus (PFH). It also has rewarding effects when injected into the nucleus accumbens (N.Acc) as evidenced by its induction of conditioned place preference (CPP) learning. To clarify the anatomical specificity of NPY's role in mediating feeding and reward, the present dissertation examined the effects of PFH ' vs.' N.Acc injections of NPY on "regulatory feeding" (resulting from homeostatic need) 'vs.' "non-regulatory feeding" (due to rewarding properties of food) as well as other reward-related behaviours. Regulatory feeding was assessed by measuring intake of a non-preferred food, powdered lab chow, while non-regulatory feeding was assessed by measuring intake of a preferred food, sucrose. Other measures of reward were performance of a progressive ratio (PR) operant response for sucrose and CPP. The contribution of dopamine (DA) in mediating these NPY-site effects was also determined. NPY dose-dependently increased chow (Experiment These results indicate an anatomical dissociation between certain behavioural effects of NPY in the PFH 'vs.' the N.Acc. The PFH mediates NPY's effects on regulatory feeding but plays little, if any, role in reward-relevant behaviours. Conversely, NPY in the N.Acc supports reward-related but not intake-enhancing effects. Further support for this conclusion comes from findings that DA does not contribute significantly to NPY's regulatory feeding response in the PFH, while its mediation of NPY reward in the N.Acc appears to exist, but is not robust.Ph.D