Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of GSK1521498 and naltrexone (NTX) on binge eating. On the top, effect of GSK15121498 on 10-min access to chow (a), 10-min access to chow or chocolate (b), access to chow in home-cage, and after the experimental session (c). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5 females, black bars) and in chow/chocolate-fed rats (n=6 females, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals; ##p<0.01 compared with vehicle-treated chow/chow-fed animals. On the bottom, effect of NTX on 10-min access to chow (d), 10-min access to chow or chocolate (e), access to chow in home-cage, and after the experimental session (f). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5, black bars) and in chow/chocolate-fed rats (n=6, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3473330&req=5

fig5: Effects of GSK1521498 and naltrexone (NTX) on binge eating. On the top, effect of GSK15121498 on 10-min access to chow (a), 10-min access to chow or chocolate (b), access to chow in home-cage, and after the experimental session (c). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5 females, black bars) and in chow/chocolate-fed rats (n=6 females, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals; ##p<0.01 compared with vehicle-treated chow/chow-fed animals. On the bottom, effect of NTX on 10-min access to chow (d), 10-min access to chow or chocolate (e), access to chow in home-cage, and after the experimental session (f). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5, black bars) and in chow/chocolate-fed rats (n=6, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals.

Mentions: Under the vehicle condition, chow/chocolate-fed rats showed anticipatory chow hypophagia and chocolate pellet hyperphagia. Treatment with GSK1521498 differentially affected the first 10-min chow intake according to diet history (main effect of diet history: (F(1,9)=5.5; p=0.043) and a diet historyXdose interaction: (F(3,27)=6.1; p=0.006)). Thus, GSK1521498 treatment resulted in increased chow intake in chow/chocolate-fed rats and decreased chow intake in chow/chow-fed rats in a dose-dependent manner, ie, it abolished anticipatory chow hypophagia. Post hoc analysis revealed a significant increase in chow intake in chow/chocolate-fed rats treated with 3 mg/kg GSK1521498 (p<0.05). GSK1521498 also differentially affected the second 10-min chocolate intake according to diet history (main effect of diet history: (F(1,9)=508.2; p<0.001) and a diet historyXdose interaction: (F(3,27)=3.1; p=0.043). Thus, GSK1521498 treatment dose dependently resulted in a decreased chocolate intake in chow/chocolate-fed rats (main effect of dose: (F(3,27)=3.2; p=0.038)). Post hoc analysis revealed a significant decrease in chocolate intake from the second chocolate feeder at the 1 mg/kg (p<0.05) and 3 mg/kg (p<0.05) doses of GSK1521498. GSK1521498 also differentially decreased chow intake in the home-cage according to diet history (main effect of dose: (F(3,27)=31.4; p<0.001) and main effect of diet history: (F(1,9)=27.5; p=0.001)). Post hoc analysis revealed a significant decrease in home-cage chow intake in chow/chocolate-fed rats treated with GSK1521498 1 mg/kg (p<0.05) and 3 mg/kg (p=0.001) and also in chow/chow-fed rats treated with GSK1521498 3 mg/kg (p=0.002; Figures 5a–c).


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)

Effects of GSK1521498 and naltrexone (NTX) on binge eating. On the top, effect of GSK15121498 on 10-min access to chow (a), 10-min access to chow or chocolate (b), access to chow in home-cage, and after the experimental session (c). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5 females, black bars) and in chow/chocolate-fed rats (n=6 females, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals; ##p<0.01 compared with vehicle-treated chow/chow-fed animals. On the bottom, effect of NTX on 10-min access to chow (d), 10-min access to chow or chocolate (e), access to chow in home-cage, and after the experimental session (f). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5, black bars) and in chow/chocolate-fed rats (n=6, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Effects of GSK1521498 and naltrexone (NTX) on binge eating. On the top, effect of GSK15121498 on 10-min access to chow (a), 10-min access to chow or chocolate (b), access to chow in home-cage, and after the experimental session (c). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5 females, black bars) and in chow/chocolate-fed rats (n=6 females, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals; ##p<0.01 compared with vehicle-treated chow/chow-fed animals. On the bottom, effect of NTX on 10-min access to chow (d), 10-min access to chow or chocolate (e), access to chow in home-cage, and after the experimental session (f). Values represent the averaged caloric intakes (kcal) (±SEM) in chow/chow-fed animals (n=5, black bars) and in chow/chocolate-fed rats (n=6, white bars). *p<0.05, **p<0.01 compared with vehicle-treated chow/chocolate-fed animals.
Mentions: Under the vehicle condition, chow/chocolate-fed rats showed anticipatory chow hypophagia and chocolate pellet hyperphagia. Treatment with GSK1521498 differentially affected the first 10-min chow intake according to diet history (main effect of diet history: (F(1,9)=5.5; p=0.043) and a diet historyXdose interaction: (F(3,27)=6.1; p=0.006)). Thus, GSK1521498 treatment resulted in increased chow intake in chow/chocolate-fed rats and decreased chow intake in chow/chow-fed rats in a dose-dependent manner, ie, it abolished anticipatory chow hypophagia. Post hoc analysis revealed a significant increase in chow intake in chow/chocolate-fed rats treated with 3 mg/kg GSK1521498 (p<0.05). GSK1521498 also differentially affected the second 10-min chocolate intake according to diet history (main effect of diet history: (F(1,9)=508.2; p<0.001) and a diet historyXdose interaction: (F(3,27)=3.1; p=0.043). Thus, GSK1521498 treatment dose dependently resulted in a decreased chocolate intake in chow/chocolate-fed rats (main effect of dose: (F(3,27)=3.2; p=0.038)). Post hoc analysis revealed a significant decrease in chocolate intake from the second chocolate feeder at the 1 mg/kg (p<0.05) and 3 mg/kg (p<0.05) doses of GSK1521498. GSK1521498 also differentially decreased chow intake in the home-cage according to diet history (main effect of dose: (F(3,27)=31.4; p<0.001) and main effect of diet history: (F(1,9)=27.5; p=0.001)). Post hoc analysis revealed a significant decrease in home-cage chow intake in chow/chocolate-fed rats treated with GSK1521498 1 mg/kg (p<0.05) and 3 mg/kg (p=0.001) and also in chow/chow-fed rats treated with GSK1521498 3 mg/kg (p=0.002; Figures 5a–c).

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