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The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

ABSTRACT: Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

SUBMITTER: Feltmann K

PROVIDER: S-EPMC5770763 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

Feltmann Kristin K Giuliano Chiara C Everitt Barry J BJ Steensland Pia P Alsiö Johan J

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170912 3

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 ...[more]

PMID: 28895569

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Project description:BackgroundCurrent guidelines recommend cognitive behavior therapy (CBT) as the treatment of choice for binge eating disorder (BED). Although CBT is quite effective, a substantial number of patients do not reach abstinence from binge eating. To tackle this problem, various theoretical conceptualizations and treatment models have been proposed. Dialectical behavior therapy (DBT), focusing on emotion regulation, is one such model. Preliminary evidence comparing DBT adapted for BED (DBT-BED) to CBT is promising but the available data do not favor one treatment over the other. The aim of this study is to evaluate outcome of DBT-BED, compared to a more intensive eating disorders-focused form of cognitive behavior therapy (CBT+), in individuals with BED who are overweight and engage in emotional eating.MethodsSeventy-four obese patients with BED who reported above average levels of emotional eating were quasi-randomly allocated to one of two manualized 20-session group treatments: DBT-BED (n = 41) or CBT+ (n = 33). Intention-to-treat outcome was examined at post-treatment and at 6-month follow-up using general or generalized linear models with multiple imputation.ResultsOverall, greater improvements were observed in CBT+. Differences in number of objective binge eating episodes at end of treatment, and eating disorder psychopathology (EDE-Q Global score) and self-esteem (EDI-3 Low Self-Esteem) at follow-up reached statistical significance with medium effect sizes (Cohen's d between .46 and .59). Of the patients in the DBT group, 69.9% reached clinically significant change at end of the treatment vs 65.0% at follow-up. Although higher, this was not significantly different from the patients in the CBT+ group (52.9% vs 45.8%).ConclusionsThe results of this study show that CBT+ produces better outcomes than the less intensive DBT-BED on several measures. Yet, regardless of the dose-difference, the data suggest that DBT-BED and CBT+ lead to comparable levels of clinically meaningful change in global eating disorder psychopathology. Future recommendations include the need for dose-matched comparisons in a sufficiently powered randomized controlled trial, and the need to determine mediators and moderators of treatment outcome.Trial registrationNederlands Trial Register: NL3982 (NTR4154). Date of registration: 2013 August 28, retrospectively registered.

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:Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell ("frustration stress"). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg-1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

Dataset Information

The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

Publications

The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

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