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

ABSTRACT: Endogenous opioids, and in particular ?-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 ?-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 ?-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.

SUBMITTER: Giuliano C

PROVIDER: S-EPMC3473330 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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

Giuliano Chiara C Robbins Trevor W TW Nathan Pradeep J PJ Bullmore Edward T ET Everitt Barry J BJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20120718 12

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 ...[more]

PMID: 22805601

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Project description:Eating disorders (EDs) and substance use disorders (SUDs) commonly co-occur, especially in conjunction with affective syndromes, yet little is known about opiate abuse and ED symptoms in patients on naltrexone-bupropion therapy. Moreover, evidence suggests that the opioid system can also be regarded as one of the major systems regulating the anticipatory processes preceding binge eating episodes. The lack of evidence in the effectiveness of psychotherapy treatment in addition to psychotropic mediations compounds the difficulties in stabilizing individuals with EDs. This article aims to exhaustively review literature relating to the use of opioid antagonists in the management of binge eating disorder (BED) and other abnormal eating habits and how this can be augmented by the use of psychological approaches to come up with the most effective therapy or combination of therapies to manage these conditions. Although this approach is promising, it has not been evaluated. A review of the literature pertaining to the use of naltrexone in patients with EDs was performed through PubMed, PsycINFO and MEDLINE. We selected 63 relevant articles published between 1981 and 2018 and those written in English. Search terms included "Opioid antagonists", "naltrexone", "bupropion" and "Psychotherapy" each combined with "Binge Eating Disorder", "Bulimia Nervosa", "Anorexia Nervosa", "Eating Disorder", "EDNOS" and "Obesity". While working with these articles, we also identified several problems related to use of these methods in real clinical practice. Seventy-seven articles were reviewed, and 63 were selected for inclusion. Data obtained from these sources confirmed that the blockade of opioid receptors diminishes food intake. More recent findings also indicate that the combination of bupropion and naltrexone can induce weight loss. Augmentation of this by introducing psychotherapy may lead to better outcomes. Cognitive behavioral therapy (CBT) was the most frequently recommended psychotherapy intervention, showing efficacy for EDs and chemical addictions as documented by most of the studies, but with uncertain efficacy when utilized as augmentation strategy. There are limited data supporting the use of psychotherapy in augmentation of standard therapy in ED; however, there is evidence to support that psychotherapy is safe in this population and has been effective in cases of patients with opiate addiction with and without psychiatric comorbidities as well as BED. More research is needed to establish treatment guidelines. Combining pharmacotherapeutic and psychotherapeutic interventions leads to the achievement of a better outcome in managing patients with EDs. Involving families or the use of support groups increases chances of adherence to the prescribed interventions resulting in higher rates of remission. However, it is clear that all of these interventions must occur in the context of a comprehensive treatment program. We believe that patient-specific psychotherapy may not only facilitate the treatment process, but also cause significant alterations in eating pattern. This approach for BED may lead to more significant treatment outcomes, but this possibility must be tested in larger samples.

Project description:Depressive symptoms and binge eating are both prevalent in weight management populations and may be associated with reduced benefit from behavioral weight loss, including higher attrition, more perceived barriers, lower weight loss, and increased weight regain. These two potential risk factors for poor behavioral weight loss outcomes may also be associated with each other as depressive symptoms may trigger binge eating, and binge eating-related distress could increase depressive symptoms. The depressive symptom-binge eating link has not been well studied in weight management samples, and psychological processes involved in this relationship have not yet been elucidated. Psychological flexibility, an individual's ability to be connected with and conscious of the present moment and to engage in values-consistent behavior even in the presence of difficult internal experiences, may be one psychological process that changes the depressive symptom-binge eating relationship. High psychological flexibility may be a protective factor in the association of depressive symptoms with binge eating. This study examined the relationship between depressive symptom and binge eating and a potential interactive role of psychological flexibility. Participants (N = 468, 76% female) completed self-report questionnaires of binge eating, depressive symptoms, and psychological flexibility at baseline prior to initiating behavioral weight loss. Depressive symptoms were positively associated with binge eating (B = 1.00, p < 0.001). Psychological flexibility had an interactive role (B = -0.03, p = 0.005). Among participants with minimal to mild depressive symptoms, those with higher psychological flexibility had less severe binge eating. Findings suggest that psychological flexibility may be a protective factor in the association between depressive symptoms and binge eating in the majority of individuals initiating behavioral weight loss. Psychological flexibility is a psychological process to consider targeting for enhancing efficacy of weight loss treatment, especially among individuals with minimal to mild depressive symptoms and binge eating behavior.

Project description:Background and purposeThe macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro-Phe-Trp]) is a multifunctional μ-opioid receptor and κ-opioid receptor agonist and κ-opioid receptor antagonist that produces antinociception and prevents stress-induced reinstatement of extinguished cocaine-conditioned place preference (CPP). We hypothesized that an analogue of CJ-15,208, cyclo[Pro-Sar-Phe-d-Phe], would demonstrate multifunctional μ-opioid receptor and κ-opioid receptor ligand activity, producing potent antinociception with fewer liabilities than selective μ-opioid receptor agonists, while preventing both drug- and stress-induced reinstatement of morphine-induced CPP.Experimental approachThe opioid receptor agonist and antagonist activity of cyclo[Pro-Sar-Phe-d-Phe] was characterized after i.c.v. and i.p. administration to C57BL/6J or transgenic opioid receptor "knockout" mice using the 55°C warm-water tail-withdrawal assay. Liabilities of locomotor coordination, respiration and spontaneous ambulation, and direct rewarding or aversive properties were assessed. Finally, the ability of cyclo[Pro-Sar-Phe-d-Phe] to block morphine- and stress-induced reinstatement of extinguished CPP was determined.Key resultscyclo[Pro-Sar-Phe-d-Phe] demonstrated dose-dependent, short-lasting antinociception, with an ED50 (and 95% confidence interval) of 0.15 (0.05-0.21) nmol i.c.v. and 1.91 (0.40-3.54) mg·kg-1 i.p., mediated by μ- and κ-opioid receptors. The macrocyclic tetrapeptide also demonstrated potent dose-dependent κ-opioid receptor antagonist-like activity at 2.5, but not at 4.5, h after administration. cyclo[Pro-Sar-Phe-d-Phe] displayed reduced liabiities compared with morphine, attributed to its additional activity at κ-receptors. Pretreatment with cyclo[Pro-Sar-Phe-d-Phe] prevented stress- and drug-induced reinstatement of extinguished morphine-place preference responses in a time-dependent manner.Conclusions and implicationsThese data suggest that cyclo[Pro-Sar-Phe-d-Phe] is a promising lead compound for both the treatment of pain with reduced sideeffects and preventing both drug- and stress-induced relapse in morphine-abstinent subjects.

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

Publications

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

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