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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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Food preference. Male (n=6) and female (n=6) rats were provided with concurrent access to chow diet and to chocolate-flavoured pellets in the home-cage for 15 consecutive days. Chow and chocolate pellets left in the home-cage were weighed every 24-h. Data are expressed as the averaged % of total 24-h (kcal) intake (±SEM) consumed in the form of the chocolate-flavoured pellets by females (open circles) and males (closed circles) (a). On the right, the first two bars show the means of chow (white) and chocolate (black) preference over 14 days in males. The second set of two bars show the means of chow (white) and chocolate (black) preference over 14 days in females (b). *p<0.05 compared with chocolate preference.
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fig1: Food preference. Male (n=6) and female (n=6) rats were provided with concurrent access to chow diet and to chocolate-flavoured pellets in the home-cage for 15 consecutive days. Chow and chocolate pellets left in the home-cage were weighed every 24-h. Data are expressed as the averaged % of total 24-h (kcal) intake (±SEM) consumed in the form of the chocolate-flavoured pellets by females (open circles) and males (closed circles) (a). On the right, the first two bars show the means of chow (white) and chocolate (black) preference over 14 days in males. The second set of two bars show the means of chow (white) and chocolate (black) preference over 14 days in females (b). *p<0.05 compared with chocolate preference.

Mentions: All the rats receiving concurrent ad libitum access to chow diet and to iso-caloric chocolate-flavoured pellets in the home-cage for 15 consecutive days showed preference for chocolate-flavoured pellets (males: 74.93±9.57% vs females: 88.58±3.46%) on the first day, and there were no differences between males and females (t(10)=1.34; NS). However, starting from the second day, female rats showed a clear preference for chocolate-flavoured pellets while male rats did not (repeated measures ANOVA revealed a main effect of time: (F(13,130)=2.6; p=0.003) and a timeXsex interaction: (F(13,130)=1.8; p=0.051; Figure 1a). Moreover, there was no difference in chocolate and chow intake from day 2 to 15 in males (t(5)=0.59; NS), but there was an increase in chocolate compared with chow intake in females (t(5)=3.51; p=0.017; Figure 1b).


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)

Food preference. Male (n=6) and female (n=6) rats were provided with concurrent access to chow diet and to chocolate-flavoured pellets in the home-cage for 15 consecutive days. Chow and chocolate pellets left in the home-cage were weighed every 24-h. Data are expressed as the averaged % of total 24-h (kcal) intake (±SEM) consumed in the form of the chocolate-flavoured pellets by females (open circles) and males (closed circles) (a). On the right, the first two bars show the means of chow (white) and chocolate (black) preference over 14 days in males. The second set of two bars show the means of chow (white) and chocolate (black) preference over 14 days in females (b). *p<0.05 compared with chocolate preference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Food preference. Male (n=6) and female (n=6) rats were provided with concurrent access to chow diet and to chocolate-flavoured pellets in the home-cage for 15 consecutive days. Chow and chocolate pellets left in the home-cage were weighed every 24-h. Data are expressed as the averaged % of total 24-h (kcal) intake (±SEM) consumed in the form of the chocolate-flavoured pellets by females (open circles) and males (closed circles) (a). On the right, the first two bars show the means of chow (white) and chocolate (black) preference over 14 days in males. The second set of two bars show the means of chow (white) and chocolate (black) preference over 14 days in females (b). *p<0.05 compared with chocolate preference.
Mentions: All the rats receiving concurrent ad libitum access to chow diet and to iso-caloric chocolate-flavoured pellets in the home-cage for 15 consecutive days showed preference for chocolate-flavoured pellets (males: 74.93±9.57% vs females: 88.58±3.46%) on the first day, and there were no differences between males and females (t(10)=1.34; NS). However, starting from the second day, female rats showed a clear preference for chocolate-flavoured pellets while male rats did not (repeated measures ANOVA revealed a main effect of time: (F(13,130)=2.6; p=0.003) and a timeXsex interaction: (F(13,130)=1.8; p=0.051; Figure 1a). Moreover, there was no difference in chocolate and chow intake from day 2 to 15 in males (t(5)=0.59; NS), but there was an increase in chocolate compared with chow intake in females (t(5)=3.51; p=0.017; Figure 1b).

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