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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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Related in: MedlinePlus

Effect of naltrexone (NTX) on food seeking. Effects of NTX on food-seeking under a second-order schedule of reinforcement during the first food-free interval (a, b) and after food delivery (second interval) (c, d) in male (n=6, gray bars) and in female (n=6, white bars) rats. Data shown are mean (±SEM) number of presses on the active (a, c) and inactive lever (b, d). *p<0.05 compared with vehicle-treated animals.
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fig3: Effect of naltrexone (NTX) on food seeking. Effects of NTX on food-seeking under a second-order schedule of reinforcement during the first food-free interval (a, b) and after food delivery (second interval) (c, d) in male (n=6, gray bars) and in female (n=6, white bars) rats. Data shown are mean (±SEM) number of presses on the active (a, c) and inactive lever (b, d). *p<0.05 compared with vehicle-treated animals.

Mentions: In both males and females, treatment with NTX was without effect on responding during the first interval of the session (no main effect of dose: (F(3,30)=1.3; NS); no main effect of sex: (F(3,30)=0.9;. NS)). After chocolate pellets delivery in the second interval, NTX-treated subjects had decreased responding in a dose-dependent manner (F(3,30)=6.7; p=0.001). Post hoc analysis revealed a significant decrease in food seeking after treatment with 0.1, 1, and 3 mg/kg during the post-ingestive second interval of the session in both males and females (Figure 3).


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)

Effect of naltrexone (NTX) on food seeking. Effects of NTX on food-seeking under a second-order schedule of reinforcement during the first food-free interval (a, b) and after food delivery (second interval) (c, d) in male (n=6, gray bars) and in female (n=6, white bars) rats. Data shown are mean (±SEM) number of presses on the active (a, c) and inactive lever (b, d). *p<0.05 compared with vehicle-treated animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Effect of naltrexone (NTX) on food seeking. Effects of NTX on food-seeking under a second-order schedule of reinforcement during the first food-free interval (a, b) and after food delivery (second interval) (c, d) in male (n=6, gray bars) and in female (n=6, white bars) rats. Data shown are mean (±SEM) number of presses on the active (a, c) and inactive lever (b, d). *p<0.05 compared with vehicle-treated animals.
Mentions: In both males and females, treatment with NTX was without effect on responding during the first interval of the session (no main effect of dose: (F(3,30)=1.3; NS); no main effect of sex: (F(3,30)=0.9;. NS)). After chocolate pellets delivery in the second interval, NTX-treated subjects had decreased responding in a dose-dependent manner (F(3,30)=6.7; p=0.001). Post hoc analysis revealed a significant decrease in food seeking after treatment with 0.1, 1, and 3 mg/kg during the post-ingestive second interval of the session in both males and females (Figure 3).

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