title: Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict.
abstract: Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55-102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss.
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI; Department of Nutrition and Food Science, Wayne State University, Detroit, MI. Electronic address: paul.burghardt@wayne.edu.
authors.forename: P R
authors.initials: PR
authors.lastname: Burghardt
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: D M
authors.initials: DM
authors.lastname: Krolewski
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: K E
authors.initials: KE
authors.lastname: Dykhuis
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: J
authors.initials: J
authors.lastname: Ching
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: A M
authors.initials: AM
authors.lastname: Pinawin
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI.
authors.forename: S L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: L G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI; Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: S J
authors.initials: SJ
authors.lastname: Watson
authors.affiliation: Department of Psychiatry, University of Michigan, Ann Arbor, MI; Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI.
authors.forename: H
authors.initials: H
authors.lastname: Akil
mesh_terms: D000818:Animals; D004435:Eating / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005215:Fasting / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D054439:Ghrelin; D020738:Leptin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
keywords: Behavior; Conflict; Ingestion; Metabolism; Novelty