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. 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.

Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal

“…Moreover, we found that mice withdrawn from a palatable HFD showed a small, yet consistent drop in body weight, which is a reported physiological response to a heightened-stress-state associated with reductions in rewarding stimuli. 25,42 Several lines of evidence indicate that, increased stress and anxiety triggers relapse to drug [43][44][45] and food seeking, 46,47 and thus we posit that the stressful effects of diet withdrawal contribute to the increased motivation for sucrose and fat we observed. Chronic high-fat feeding and withdrawal produced several changes in DA and plasticity-related proteins in the amygdala and NAc, and to lesser extent in the VTA, that are tied to lasting neurochemical and behavioural changes related to dopaminergic function.…”

Yohimbine impairs extinction of cocaine-conditioned place preference in an α2-adrenergic receptor independent process

“…It has been recently used in the study of reinstatement of positive valence behaviors (Shepard et al 2004;Ledgerwood et al 2005;Ghitza et al 2006Ghitza et al , 2007. Our data suggest that yohimbine may impair extinction of the learned behavior; thus, the mice may still have a preference for the CS+ (side or lever) when tested.…”

New operant model of reinstatement of food-seeking behavior in mice

“…Pharmacological stressor We tested in our experimental conditions the effects induced by yohimbine, an α-2 adrenoceptor antagonist that provokes anxiety-like responses (Bremner et al 1996) and reinstates drug-and food-seeking in rats (Lê et al 1998;Ghitza et al 2006Ghitza et al , 2007Nair et al 2006). At the dose tested in the present study (2 mg/kg, i.p.…”

“…The yohimbine doses (1, 2, and 4 mg/kg, i.p.) were chosen based on previous studies reported in the literature (Shimada et al 1995;Blanchard et al 2001;Ghitza et al 2006Ghitza et al , 2007.…”