title: Lisdexamfetamine reduces the compulsive and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model.
abstract: Compulsive and perseverative behaviour in binge-eating, female, Wistar rats was investigated in a novel food reward/punished responding conflict model. Rats were trained to perform the conditioned avoidance response task. When proficient, the paradigm was altered to a food-associated conflict test by placing a chocolate-filled jar (empty jar for controls) in one compartment of the shuttle box. Entry into the compartment with the jar triggered the conditioning stimulus after a variable interval, and foot-shock 10 seconds later if the rat did not leave. Residence in the 'safe' compartment with no jar did not initiate trials or foot-shocks. By frequently entering the chocolate-paired compartment, binge-eating rats completed their 10 trials more quickly than non-binge controls. Binge-eating rats spent a greater percentage of the session in the chocolate-paired compartment, received foot-shocks more frequently, and tolerated foot-shocks for longer periods; all consistent with compulsive and perseverative behaviour. The d-amphetamine prodrug, lisdexamfetamine, has recently received US approval for the treatment of moderate to severe binge-eating disorder in adults. Lisdexamfetamine (0.8 mg/kg po [d-amphetamine base]) decreased chocolate consumption by binge-eating rats by 55% and markedly reduced compulsive and perseverative responding in the model. These findings complement clinical results showing lisdexamfetamine reduced compulsiveness scores in subjects with binge-eating disorder.
authors.affiliation: RenaSci Ltd., BioCity, Nottingham, UK david.heal@renasci.co.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
authors.affiliation: RenaSci Ltd., BioCity, Nottingham, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Goddard
authors.affiliation: RenaSci Ltd., BioCity, Nottingham, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brammer
authors.affiliation: Shire Development Inc., Lexington, MA, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.affiliation: RenaSci Ltd., BioCity, Nottingham, UK.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Vickers
mesh_terms: D000818:Animals; D056912:Binge-Eating Disorder / Q000188:drug therapy*; D002032:Bulimia / Q000188:drug therapy*; D003192:Compulsive Behavior / Q000188:drug therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D000069478:Lisdexamfetamine Dimesylate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D000069478:Lisdexamfetamine Dimesylate
keywords: Lisdexamfetamine; binge eating; compulsive; conflict model; perseverative