Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 43, Pages 11522-11532Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5405-06.2007
Keywords
arcuate nucleus; heroin self-administration; peptide YY; reinstatement; relapse; stress; Y2 receptors; yohimbine
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Funding
- Intramural NIH HHS [Z01 DA000434-08] Funding Source: Medline
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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 mu g/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 mu g 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 mu g 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.
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