Two of the greatest threats to public health in the United States are drug addiction and obesity. The neural circuits effected by rewarding drugs and presumed to be altered in addiction are the very same pathways that regulate the intake of our most important natural reward, food. Indeed, the neural system most clearly implicated in drug addiction is the nucleus accumbens and associated circuitry. This region also has been shown to subserve motivated behaviors such as feeding, drinking, sexual behavior, and incentive learning. This research proposal focuses on the role of endogenous opioids within the ventral striatum (nucleus accumbens and surrounding striatal regions) in mediating the rewarding properties of food. Considerable evidence suggests that ventral striatal opioids specifically mediate palatability and the hedonic (affective) aspects of feeding. Previous work has shown that intra-accumbens administration of the mu-opioid agonist D-Ala2, Nme-Phe4, Glyol 5-enkephalin (DAMGO) markedly increases food intake and preferentially enhances the intake of highly palatable substances. The proposed studies here will integrate behavioral analysis, microinjection mapping, and in-situ hybridization methodology to further investigate these phenomena.
| Will, Matthew J; Pratt, Wayne E; Kelley, Ann E (2006) Pharmacological characterization of high-fat feeding induced by opioid stimulation of the ventral striatum. Physiol Behav 89:226-34 |
| Kelley, Ann E; Baldo, Brian A; Pratt, Wayne E et al. (2005) Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773-95 |
| Will, Matthew J; Franzblau, Emily B; Kelley, Ann E (2004) The amygdala is critical for opioid-mediated binge eating of fat. Neuroreport 15:1857-60 |
| Will, M J; Franzblau, E B; Kelley, A E (2003) Nucleus accumbens mu-opioids regulate intake of a high-fat diet via activation of a distributed brain network. J Neurosci 23:2882-8 |
| Kelley, A E; Will, M J; Steininger, T L et al. (2003) Restricted daily consumption of a highly palatable food (chocolate Ensure(R)) alters striatal enkephalin gene expression. Eur J Neurosci 18:2592-8 |
