title: Dopamine and μ-opioid receptor dysregulation in the brains of binge-eating female rats - possible relevance in the psychopathology and treatment of binge-eating disorder.
abstract: Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D1receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors. There was no change in D1receptor density in nucleus accumbens, medial prefrontal cortex or dorsolateral frontal cortex, striatal D2receptors and dopamine reuptake transporter sites, or μ-opioid receptors in frontal cortex. There were no changes in ligand affinities. The concentrations of monoamines, metabolites and estimates of dopamine (dopamine/dihydroxyphenylacetic acid ratio) and serotonin/5-hydroxyindolacetic acid ratio turnover rates were unchanged in striatum and frontal cortex. However, turnover of dopamine and serotonin in the hypothalamus was increased ~20% and ~15%, respectively. Striatal transmission via D1receptors is decreased in binge-eating rats while μ-opioid receptor signalling may be increased. These changes are consistent with the attenuation of binge-eating by lisdexamfetamine, which increases catecholaminergic neurotransmission, and nalmefene, a μ-opioid antagonist.
authors.affiliation: 1 RenaSci Ltd, Nottingham, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
authors.affiliation: 1 RenaSci Ltd, Nottingham, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hallam
authors.affiliation: 1 RenaSci Ltd, Nottingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Prow
authors.affiliation: 1 RenaSci Ltd, Nottingham, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Gosden
authors.affiliation: 1 RenaSci Ltd, Nottingham, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cheetham
authors.affiliation: 2 Department of Psychiatry and Neuroscience, Harvard Medical School, Belmont, MA, USA.
authors.forename: Yong K
authors.initials: YK
authors.lastname: Choi
authors.affiliation: 2 Department of Psychiatry and Neuroscience, Harvard Medical School, Belmont, MA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Tarazi
authors.affiliation: 3 Shire Development Inc., Lexington, MA, USA.|4 Neurobiology, Teva Pharmaceuticals, West Chester, PA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hutson
mesh_terms: D000818:Animals; D056912:Binge-Eating Disorder / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002032:Bulimia / Q000188:drug therapy / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011599:Psychopathology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D009292:Narcotic Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C038981:nalmefene; D004298:Dopamine
keywords: Binge-eating; D1 and D2 receptors; dopamine reuptake transporter sites; striatum; μ-opioid receptors