Peptide YY3-36 decreases reinstatement of high-fat food seeking during dieting in a rat relapse model

Udi E. Ghitza, Sunila G. Nair, Sam A. Golden, Sarah M. Gray, Jamie L. Uejima, Jennifer M. Bossert, Yavin Shaham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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 μg/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 μg 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 μg 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.

Original languageEnglish (US)
Pages (from-to)11522-11532
Number of pages11
JournalJournal of Neuroscience
Issue number43
StatePublished - Oct 24 2007


  • Arcuate nucleus
  • Heroin self-administration
  • Peptide YY
  • Reinstatement
  • Relapse
  • Stress
  • Y2 receptors
  • Yohimbine

ASJC Scopus subject areas

  • Neuroscience(all)


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