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The Journal of Neuroscience, October 24, 2007, 27(43):11522-11532; doi:10.1523/JNEUROSCI.5405-06.2007
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Behavioral/Systems/Cognitive
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, andYavin Shaham Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224
Correspondence should be addressed to Dr. Yavin Shaham, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: yshaham{at}intra.nida.nih.gov
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.
Key words: arcuate nucleus; heroin self-administration; peptide YY; reinstatement; relapse; stress; Y2 receptors; yohimbine
Received Dec. 14, 2006; revised Sept. 13, 2007; accepted Sept. 13, 2007.
Correspondence should be addressed to Dr. Yavin Shaham, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224. Email: yshaham{at}intra.nida.nih.gov
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[Abstract] [Full Text] [PDF]
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