Dataset Information

Antagonism of sigma-1 receptors blocks compulsive-like eating.

ABSTRACT: Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1?h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24?h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1?h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder.

SUBMITTER: Cottone P

PROVIDER: S-EPMC3473342 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antagonism of sigma-1 receptors blocks compulsive-like eating.

Cottone Pietro P Wang Xiaofan X Park Jin Won JW Valenza Marta M Blasio Angelo A Kwak Jina J Iyer Malliga R MR Steardo Luca L Rice Kenner C KC Hayashi Teruo T Sabino Valentina V

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20120620 12

Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 ope ...[more]

PMID: 22713906

Similar Datasets

Project description:Background:Dysfunctional thoughts- and use of physical activity (PA) are core symptoms of the eating disorders (ED) bulimia nervosa (BN) and binge eating disorder (BED). The compulsive desire for PA complicates a favourable treatment outcome; hence, regular, adapted PA led by personnel with competence in exercise science is rarely part of treatment of BN and BED. The present study compared cognitive behaviour therapy (CBT) with a new treatment combining physical exercise and dietary therapy (PED-t) with respect to the short- and long-term changes in the level of compulsive exercise and actual level of PA in women with BN or BED. Methods:We enrolled 187 women with BN or BED, aged 18-40 years, with BMI 17.5-35, in an outpatient randomised controlled therapy trial. Participants were randomised to PED-t or CBT, while waitlist participants served as a control group during the treatment period. The treatment covered 16 weeks, with 6- and 12 months follow-up, and outcomes included self-reported compulsive exercise (CE) and objectively measured PA, analysed by linear mixed regression models. Results:Both CBT and PED-t reduced CE from baseline (P?<?0.01, Hedges g ~?0.4), but with no difference to control group. Compared to baseline, only PED-t significantly reduced the number of patients who scored above cut-off rating for CE, but with no between-group differences. The proportion of participants complying with the official recommendation for PA neither changed following treatment, nor emerged different between the treatment arms. Conclusion:Both therapies resulted in significant improvements in compulsive exercise, a change not found in the control group, however there were no between-group differences. The findings are tempered by the low statistical power due to a small control group size. The number of participants complying with the recommendation for PA were stable throughout the study, and no change in total PA was found. Presence and intensity of CE decline with treatment, but a need to increase PA towards healthy levels remains unsolved. Trial registration:Approved by the Norwegian Regional Committee for Medical and Health Research Ethics (ID: 2013/1871, 16th of December 2013); registered in Clinical Trials (ID: NCT02079935, 17th of February 2014).

Project description:Compulsive eating behavior is hypothesized to be driven in part by reward deficits likely due to neuroadaptations to the mesolimbic dopamine (DA) system. Therefore, the aim of this study was to assess deficits in reward system functioning and mesolimbic DA after alternating a standard chow with palatable diet, a model of compulsive eating. In this model, rats in the control group (Chow/Chow) are provided a standard chow diet 7 days a week, while the experimental group (Chow/Palatable) is provided chow for 5 days a week ("C Phase"), followed by 2 days of access to a highly palatable sucrose diet ("P Phase"). We first tested the sensitivity to d-Amphetamine's stimulatory, reward-enhancing, and primary rewarding effects using a locomotor activity assay, an intracranial self-stimulation (ICSS) procedure, and a conditioned place preference test, respectively. We then quantified DA release in the nucleus accumbens (NAc) shell after treatment with d-Amphetamine using in vivo microdialysis, quantified levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA using quantitative polymerase chain reaction (qPCR), and lastly, quantified baseline extracellular DA and function of DAT in vivo using quantitative "no-net-flux" microdialysis. Chow/Palatable rats displayed blunted d-Amphetamine-induced locomotor activity, insensitivity to d-Amphetamine potentiation of ICSS threshold, and decreased place preference for d-Amphetamine during the P Phase. We found that Chow/Palatable rats had blunted DA efflux following d-Amphetamine treatment. Furthermore, DAT mRNA was increased in Chow/Palatable rats during the P Phase. Finally, quantitative "no-net-flux" microdialysis revealed reduced extracellular baseline DA and DAT function in Chow/Palatable rats. Altogether, these results provide evidence of reduced reward system functioning and related neuroadaptations in the DA and DAT systems in this model of compulsive eating. Reward deficits, resulting from repeated overeating, may in turn contribute to the perpetuation of compulsive eating behavior.

Dataset Information

Antagonism of sigma-1 receptors blocks compulsive-like eating.

Publications

Antagonism of sigma-1 receptors blocks compulsive-like eating.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets