Obesity is currently one of the major public health problems in the United States. Over 65% of the U.S. adult population is overweight. Obesity puts individuals at considerable risk for many disorders, such as heart disease, hypertension, diabetes, stroke, and certain types of cancer. Although there are a number of complex factors contributing to this trend, such as genetic predisposition, inactivity, lifestyle changes, and economic factors, the abundance and over consumption of calorically dense foods such as fats and sweets is largely responsible. Ingestion of food is required for survival, yet overabundance of energy-dense food has led to conditions that actually threaten survival. In the past decade, specific brain and peripheral systems involved in appetite control, particularly within the hypothalamus, have been discovered and characterized. However, relatively little is known about how brain networks involved in emotional regulation, executive function, and conscious control of behavior interact with hypothalamic energy balance-sensing systems. This would seem an important area of obesity research, as cognitive control, decision-making, and modulation of emotional responses in relation to the desire to eat are major determinants for the control of appetite in humans. Our work focuses on the role of the nucleus accumbens, a region within the ventral striatum, in the control of food motivation and food reward. We have shown that two main systems, one governed by endogenous opioid peptides and one by amino acid (GABA and glutamate) receptors, control certain aspects of ingestive behavior via connections with the lateral hypothalamus and other forebrain and brainstem regions.
We aim to expand these investigations to study how cortical systems (i.e. the amygdala, gustatory cortex and prefrontal cortex) interact with ventral striatum and hypothalamus in the regulation of ingestive behavior. We will employ behavioral, pharmacological, neuroanatomical and molecular methodologies to address this question within an integrated, interdisciplinary framework.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA009311-12
Application #
7194345
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Volman, Susan
Project Start
1990-08-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
12
Fiscal Year
2007
Total Cost
$241,431
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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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