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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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Effect of GSK1521498 on food seeking. Effects of GSK1521498 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, **p<0.01 compared with vehicle-treated animals.
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fig2: Effect of GSK1521498 on food seeking. Effects of GSK1521498 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, **p<0.01 compared with vehicle-treated animals.

Mentions: In total, 12 rats, 6 males and 6 females, acquired responding for highly palatable food under a second-order schedule of reinforcement, both genders making on average 500 responses during the first 15 min before the first food delivery (mean±SEM: 566.94±91.52 for males vs 457.28±56.78 for females, t(10)=1.02, NS). Treatment with GSK1521498 resulted in a significant dose-dependent decrease in responding (main effect of dose (F(3,30)=17.7; p<0.0001)) and a doseXsex interaction (F(3,30)=4.8; p=0.008) in the first (pre-ingestive) 15-min interval of the session. After reward delivery, all rats showed a dose-dependent decrease in responding (F(3,30)=17.6; p<0.001). Post hoc analysis revealed a significant decrease in food seeking in males treated with 1 and 3 mg/kg of GSK1521498, whereas in females only at 3 mg/kg during the first interval of the session. In all animals there was a decrease in responding during the post-ingestive second interval of the session at both 1 and 3 mg/kg GSK1521498 (Figure 2).


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 GSK1521498 on food seeking. Effects of GSK1521498 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, **p<0.01 compared with vehicle-treated animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Effect of GSK1521498 on food seeking. Effects of GSK1521498 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, **p<0.01 compared with vehicle-treated animals.
Mentions: In total, 12 rats, 6 males and 6 females, acquired responding for highly palatable food under a second-order schedule of reinforcement, both genders making on average 500 responses during the first 15 min before the first food delivery (mean±SEM: 566.94±91.52 for males vs 457.28±56.78 for females, t(10)=1.02, NS). Treatment with GSK1521498 resulted in a significant dose-dependent decrease in responding (main effect of dose (F(3,30)=17.7; p<0.0001)) and a doseXsex interaction (F(3,30)=4.8; p=0.008) in the first (pre-ingestive) 15-min interval of the session. After reward delivery, all rats showed a dose-dependent decrease in responding (F(3,30)=17.6; p<0.001). Post hoc analysis revealed a significant decrease in food seeking in males treated with 1 and 3 mg/kg of GSK1521498, whereas in females only at 3 mg/kg during the first interval of the session. In all animals there was a decrease in responding during the post-ingestive second interval of the session at both 1 and 3 mg/kg GSK1521498 (Figure 2).

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