title: Peptide YY3-36 decreases reinstatement of high-fat food seeking during dieting in a rat relapse model.
abstract: A major problem in treating obesity is high rates of relapse to maladaptive food-taking habits during dieting. This relapse is often provoked by acute re-exposure to palatable food, food-associated cues, or stress. We used a reinstatement model, commonly used to study relapse to abused drugs, to explore the effect of peptide YY3-36 (PYY3-36) on reinstatement of high-fat (35%, 45 mg pellets) food seeking induced by acute exposure to the pellets (pellet priming), a cue previously associated with pellet delivery (pellet cue), or yohimbine (2 mg/kg, a pharmacological stressor). Rats were placed on a restricted diet (16 g of chow per day) and lever-pressed for the pellets for 9-12 sessions (6 h/d, every 48 h); pellet delivery was paired with a tone-light cue. They were then given 10-20 extinction sessions wherein lever presses were not reinforced with the pellets and subsequently tested for reinstatement of food seeking. Systemic PYY3-36 injections (100-200 microg/kg) decreased pellet priming- and pellet cue-induced reinstatement of food seeking but not yohimbine-induced reinstatement. Arcuate nucleus (Arc) injections of PYY3-36 (0.4 microg per side) decreased pellet priming-induced reinstatement. The attenuation of pellet priming-induced reinstatement by systemic PYY3-36 was reversed by systemic (2 mg/kg) but not Arc (0.5 microg per side) injections of the Y2 receptor antagonist BIIE0246. Arc PYY3-36 injections did not decrease pellet cue-induced reinstatement. Finally, systemic PYY3-36 injections had minimal effects on ongoing food self-administration or heroin priming- or heroin cue-induced reinstatement of heroin seeking. These data identify an effect of systemic PYY3-36 on relapse to food seeking that is independent of Y2 receptor activation in Arc and suggest that PYY3-36 should be considered for the treatment of relapse to maladaptive food-taking habits during dieting.
authors.affiliation: Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
authors.forename: Udi E
authors.initials: UE
authors.lastname: Ghitza
authors.forename: Sunila G
authors.initials: SG
authors.lastname: Nair
authors.forename: Sam A
authors.initials: SA
authors.lastname: Golden
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Gray
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Uejima
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bossert
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009765:Obesity / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D055502:Secondary Prevention
chemical_list: D004041:Dietary Fats; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)