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Inhibition of opioid transmission at the μ-opioid receptor prevents both food seeking and binge-like eating.

Giuliano C, Robbins TW, Nathan PJ, Bullmore ET, Everitt BJ - Neuropsychopharmacology (2012)

Bottom Line: GSK1521498 also dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion.Thus, while both drugs affected the hedonic value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate.Selective μ-opioid receptor antagonism by GSK1521498 may have utility as a treatment for reducing maladaptive, palatability-driven eating behavior by reducing the motivational properties of stimuli that elicit the binge eating commonly associated with obesity.

View Article: PubMed Central - PubMed

Affiliation: Behavioral and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK. cg451@cam.ac.uk

ABSTRACT
Endogenous opioids, and in particular μ-opioid receptors, have been linked to hedonic and rewarding mechanisms engaged during palatable food intake. The aim of this study was to investigate the effects of GSK1521498, a novel μ-opioid receptor antagonist, on food-seeking behavior and on binge-like eating of a highly preferred chocolate diet. Food seeking was measured in rats trained to respond for chocolate under a second-order schedule of reinforcement, in which prolonged periods of food-seeking behavior were maintained by contingent presentation of a reward-associated conditioned reinforcer. After reaching a stable baseline in both procedures, animals were treated with GSK1521498 (0.1, 1, and 3 mg/kg; IP) or naltrexone (NTX, 0.1, 1, and 3 mg/kg; SC). The binge eating model was characterized by four temporally contiguous phases: 1-h chow access, 2-h food deprivation, 10-min chow access, and 10-min access to either chocolate-flavoured food or standard chow. During training the rats developed binge-like hyperphagia of palatable food and anticipatory chow hypophagia (anticipatory negative contrast). Both compounds reduced binge-like palatable food hyperphagia. However, GSK1521498 reduced the impact of high hedonic value on ingestion more specifically than NTX, abolishing anticipatory chow hypophagia. GSK1521498 also dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion. Thus, while both drugs affected the hedonic value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate. Selective μ-opioid receptor antagonism by GSK1521498 may have utility as a treatment for reducing maladaptive, palatability-driven eating behavior by reducing the motivational properties of stimuli that elicit the binge eating commonly associated with obesity.

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Binge eating paradigm. The experimental session was divided into four contiguous phases: 1-h chow access (a), 2-h food deprivation, 10-min access to chow (b), and 10-min access to chow or chocolate (c). Chow intake in the home-cage, after the experimental session, is also shown (d). Values represent the averaged intakes (kcal) from days 1–15 (±SEM), after acquisition of a stable baseline, in chow/chow-fed (n=5 females, open squares) and in chow/chocolate-fed animals (n=6 females, closed squares). **p<0.01, ***p<0.001 compared with chow/chow-fed animals.
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fig4: Binge eating paradigm. The experimental session was divided into four contiguous phases: 1-h chow access (a), 2-h food deprivation, 10-min access to chow (b), and 10-min access to chow or chocolate (c). Chow intake in the home-cage, after the experimental session, is also shown (d). Values represent the averaged intakes (kcal) from days 1–15 (±SEM), after acquisition of a stable baseline, in chow/chow-fed (n=5 females, open squares) and in chow/chocolate-fed animals (n=6 females, closed squares). **p<0.01, ***p<0.001 compared with chow/chow-fed animals.

Mentions: As only female rats developed chocolate preference, the binge eating study was conducted on females, as previously also described by Cottone et al (2008). Rats receiving highly limited access to the preferred diet (chow/chocolate) developed chow hypophagia (an ‘anticipatory negative contrast' effect) from the first feeder (main effect of diet history: (F(1,9)=11.3; p=0.008) and main effect of time: (F(14,126)=2.5; p=0.007)) and hyperphagia of the preferred diet from the second feeder (main effect of diet history: (F(1,9)=203.2; p<0.001), main effect of time: (F(14,126)=8.1; p<0.001), and a timeXdiet history interaction: (F(14,126)=9.3; p<0.001)). In addition, home-cage chow intake of chow/chocolate-fed rats was lower than that of chow/chow-fed rats (main effect diet history: (F(1,9)=17.1; p=0.003); Figure 4).


Inhibition of opioid transmission at the μ-opioid receptor prevents both food seeking and binge-like eating.

Giuliano C, Robbins TW, Nathan PJ, Bullmore ET, Everitt BJ - Neuropsychopharmacology (2012)

Binge eating paradigm. The experimental session was divided into four contiguous phases: 1-h chow access (a), 2-h food deprivation, 10-min access to chow (b), and 10-min access to chow or chocolate (c). Chow intake in the home-cage, after the experimental session, is also shown (d). Values represent the averaged intakes (kcal) from days 1–15 (±SEM), after acquisition of a stable baseline, in chow/chow-fed (n=5 females, open squares) and in chow/chocolate-fed animals (n=6 females, closed squares). **p<0.01, ***p<0.001 compared with chow/chow-fed animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473330&req=5

fig4: Binge eating paradigm. The experimental session was divided into four contiguous phases: 1-h chow access (a), 2-h food deprivation, 10-min access to chow (b), and 10-min access to chow or chocolate (c). Chow intake in the home-cage, after the experimental session, is also shown (d). Values represent the averaged intakes (kcal) from days 1–15 (±SEM), after acquisition of a stable baseline, in chow/chow-fed (n=5 females, open squares) and in chow/chocolate-fed animals (n=6 females, closed squares). **p<0.01, ***p<0.001 compared with chow/chow-fed animals.
Mentions: As only female rats developed chocolate preference, the binge eating study was conducted on females, as previously also described by Cottone et al (2008). Rats receiving highly limited access to the preferred diet (chow/chocolate) developed chow hypophagia (an ‘anticipatory negative contrast' effect) from the first feeder (main effect of diet history: (F(1,9)=11.3; p=0.008) and main effect of time: (F(14,126)=2.5; p=0.007)) and hyperphagia of the preferred diet from the second feeder (main effect of diet history: (F(1,9)=203.2; p<0.001), main effect of time: (F(14,126)=8.1; p<0.001), and a timeXdiet history interaction: (F(14,126)=9.3; p<0.001)). In addition, home-cage chow intake of chow/chocolate-fed rats was lower than that of chow/chow-fed rats (main effect diet history: (F(1,9)=17.1; p=0.003); Figure 4).

Bottom Line: GSK1521498 also dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion.Thus, while both drugs affected the hedonic value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate.Selective μ-opioid receptor antagonism by GSK1521498 may have utility as a treatment for reducing maladaptive, palatability-driven eating behavior by reducing the motivational properties of stimuli that elicit the binge eating commonly associated with obesity.

View Article: PubMed Central - PubMed

Affiliation: Behavioral and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK. cg451@cam.ac.uk

ABSTRACT
Endogenous opioids, and in particular μ-opioid receptors, have been linked to hedonic and rewarding mechanisms engaged during palatable food intake. The aim of this study was to investigate the effects of GSK1521498, a novel μ-opioid receptor antagonist, on food-seeking behavior and on binge-like eating of a highly preferred chocolate diet. Food seeking was measured in rats trained to respond for chocolate under a second-order schedule of reinforcement, in which prolonged periods of food-seeking behavior were maintained by contingent presentation of a reward-associated conditioned reinforcer. After reaching a stable baseline in both procedures, animals were treated with GSK1521498 (0.1, 1, and 3 mg/kg; IP) or naltrexone (NTX, 0.1, 1, and 3 mg/kg; SC). The binge eating model was characterized by four temporally contiguous phases: 1-h chow access, 2-h food deprivation, 10-min chow access, and 10-min access to either chocolate-flavoured food or standard chow. During training the rats developed binge-like hyperphagia of palatable food and anticipatory chow hypophagia (anticipatory negative contrast). Both compounds reduced binge-like palatable food hyperphagia. However, GSK1521498 reduced the impact of high hedonic value on ingestion more specifically than NTX, abolishing anticipatory chow hypophagia. GSK1521498 also dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion. Thus, while both drugs affected the hedonic value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate. Selective μ-opioid receptor antagonism by GSK1521498 may have utility as a treatment for reducing maladaptive, palatability-driven eating behavior by reducing the motivational properties of stimuli that elicit the binge eating commonly associated with obesity.

Show MeSH
Related in: MedlinePlus