The current 'epidemic'of obesity has been called one of the leading public health concerns worldwide. Despite recent progress in the discovery of discrete hypothalamic peptide systems that control food intake, little is known about the manner in which cognitive/affective processing coordinates with hypothalamic energy balance systems to control behavioral output. Hence, this proposal focuses on characterizing functional interactions between the medial prefrontal cortex, a brain region mediating 'executive'control over behavioral output and affective responses, and hypothalamic substrates mediating the homeostatic control of feeding. This proposal is informed by our recent discovery of a novel, specific role of medial prefrontal cortex (mPFC) in controlling feeding microstructure. We find that producing temporary lesions in mPFC fundamentally alters the manner in which rats organize behavioral responses with respect to ingestive behavior.
We aim to investigate the behavioral mechanisms and anatomical specificity associated with this effect, and to examine how inactivating mPFC influences the response to hypothalamic administration of orexigenic and anorexic peptides. To obtain a functional anatomical correlate of these behavioral studies, we will investigate the manner in which temporary lesions of the mPFC alter brain activation (measured using Fos expression) associated with feeding. Relevance to public health: These studies have the potential to reveal how the parts of the brain controlling decision-making and impulsivity (such as the prefrontal cortex) can interact with, and perhaps overwhelm, the systems that regulate food intake in response to energy needs. This could lead to fundamentally dysregulated feeding behavior. It is interesting that brain imaging studies have shown alterations in prefrontal cortex function in association with eating disorders and obesity. Our work may help understand how these cortical alterations are ultimately translated into behavioral changes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Vicentic, Aleksandra
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University of Wisconsin Madison
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United States
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Selleck, Ryan A; Baldo, Brian A (2017) Feeding-modulatory effects of mu-opioids in the medial prefrontal cortex: a review of recent findings and comparison to opioid actions in the nucleus accumbens. Psychopharmacology (Berl) 234:1439-1449
Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken et al. (2016) GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding. Neuropsychopharmacology 41:960-70
Baldo, Brian A (2016) Prefrontal Cortical Opioids and Dysregulated Motivation: A Network Hypothesis. Trends Neurosci 39:366-377
Selleck, Ryan A; Lake, Curtis; Estrada, Viridiana et al. (2015) Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action. Neuropsychopharmacology 40:2464-74
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
Mena, Jesus D; Selleck, Ryan A; Baldo, Brian A (2013) Mu-opioid stimulation in rat prefrontal cortex engages hypothalamic orexin/hypocretin-containing neurons, and reveals dissociable roles of nucleus accumbens and hypothalamus in cortically driven feeding. J Neurosci 33:18540-52
Baldo, Brian A; Pratt, Wayne E; Will, Matthew J et al. (2013) Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior. Neurosci Biobehav Rev 37:1985-98
Baldo, Brian A; Hanlon, Erin C; Obermeyer, William et al. (2013) Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss. Neuropsychopharmacology 38:2578-87
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
Mena, Jesus D; Sadeghian, Ken; Baldo, Brian A (2011) Induction of hyperphagia and carbohydrate intake by ?-opioid receptor stimulation in circumscribed regions of frontal cortex. J Neurosci 31:3249-60

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