Two of the greatest threats to public health in the United States as we enter the next century are drug addiction and obesity. Annual deaths attributable to nicotine and alcohol dependence alone are estimated at 450,000. Moreover, the surgeon general has noted that .."""""""" after smoking, weight related conditions are the second leading cause of death in the U.S. resulting in about 300,000 lives lost each year..."""""""" These individuals are at greatly elevated risk for many disorders, such as heart disease, hypertension, and diabetes. While these two health issues do not appear related in terms of etiology or phenomenology, they share important commonalities. The neural circuits affected by rewarding drugs and presumed to be profoundly altered in addiction are the very pathways that control intake of our most vital natural reward, food. The neural system most clearly implicated in drug addiction con stitutes the ventral striaturn (includin nucleus accumbens) and its associated circuitry, a region that also subserves motivated behaviors, such as feeding, drinking, sexual behavior, and incentive learning. In order to develop successful treatments for addiction and eating disorders, it is necessary to further understand the biological mechanisms underlying motivation. Specifically, it would be useful to investigate in detail the neural mecahnisms underlying the hedonic aspects of eating (""""""""food reward""""""""). The research proposed here will address this question, integrating behavioral, pharmacological, anatomical and molecular biological (in situ hybridization) techniques. The main hypothesis that guides the proposed experiments is that opioid systems, particularly in the ventral striaturn, play a critical role in an animal's affective response to food; that is in the """"""""liking"""""""" process, or the orosensory pleasure derived from highly palatable foods. It is further proposed that the ventral striaturn is a key brain region where peripheral metabolic neurohumoral signals are integrated with central control of motivational states and adaptive responding. In these experiments, we will analyze the role of signal transduction pathways, enkephalin gene expression, and circulating insulin in opioid-mediated feeding, and will also examine organization of underlying circuitries that may be involved in processing of palatability signals.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-1 (01))
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Volman, Susan
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University of Wisconsin Madison
Schools of Medicine
United States
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Perry, Michelle L; Pratt, Wayne E; Baldo, Brian A (2014) Overlapping striatal sites mediate scopolamine-induced feeding suppression and mu-opioid-mediated hyperphagia in the rat. Psychopharmacology (Berl) 231:919-28
Newman, Sarah; Pascal, Lindsay; Sadeghian, Ken et al. (2013) Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell. Biol Psychiatry 73:843-50
Perry, Michelle L; Andrzejewski, Matthew E; Bushek, Susan M et al. (2010) Intra-accumbens infusion of a muscarinic antagonist reduces food intake without altering the incentive properties of food-associated cues. Behav Neurosci 124:44-54
Perry, Michelle L; Baldo, Brian A; Andrzejewski, Matthew E et al. (2009) Muscarinic receptor antagonism causes a functional alteration in nucleus accumbens mu-opiate-mediated feeding behavior. Behav Brain Res 197:225-9
Meredith, Gloria E; Baldo, Brian A; Andrezjewski, Matthew E et al. (2008) The structural basis for mapping behavior onto the ventral striatum and its subdivisions. Brain Struct Funct 213:17-27
Pratt, Wayne E; Spencer, Robert C; Kelley, Ann E (2007) Muscarinic receptor antagonism of the nucleus accumbens core causes avoidance to flavor and spatial cues. Behav Neurosci 121:1215-23
Baldo, Brian A; Kelley, Ann E (2007) Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl) 191:439-59
Will, Matthew J; Vanderheyden, William M; Kelley, Ann E (2007) Striatal opioid peptide gene expression differentially tracks short-term satiety but does not vary with negative energy balance in a manner opposite to hypothalamic NPY. Am J Physiol Regul Integr Comp Physiol 292:R217-26
Baldo, Brian A; Alsene, Karen M; Negron, Alejandro et al. (2005) Hyperphagia induced by GABAA receptor-mediated inhibition of the nucleus accumbens shell: dependence on intact neural output from the central amygdaloid region. Behav Neurosci 119:1195-206
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

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