title: A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.
abstract: Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM) display signatures of hedonic feeding including bingeing and altered DA receptor (R) numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day) exposure to the IAM, rats given 8-12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR). This activation was negatively correlated with orexin (Orx) neuron activation in the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day) access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior. Specifically, long-term fructose bingeing activates a hyperphagic circuit composed in part of NAc shell and LH/PeF Orx neurons.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Jacki M
authors.initials: JM
authors.lastname: Rorabaugh
authors.affiliation: Rocky Mountain Taste and Smell Center, Department of Cell and Developmental Biology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Stratford
authors.affiliation: Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Zahniser
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005247:Feeding Behavior; D005632:Fructose / Q000008:administration & dosage*; D007026:Hypothalamic Area, Lateral / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000473:pathology*; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013997:Time Factors
chemical_list: C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005632:Fructose
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