title: Investigation of impulsivity in binge-eating rats in a delay-discounting task and its prevention by the d-amphetamine prodrug, lisdexamfetamine.
abstract: Freely-fed, female, rats were trained in a two-lever, delay-discounting task: one lever delivered a single chocolate-flavoured pellet immediately and the other a three-pellet reward after increasing delay (0, 4, 8, 16, 32 s). Rats were divided into two groups (i.e. binge-eating rats given irregular, limited access to chocolate in addition to normal chow and controls maintained on normal chow). Both groups exhibited increased preference for the immediate reward as the delay interval was lengthened. The discounting rate was significantly greater in binge-eating rats than non-binge-eating controls, especially as the behaviour became more established indicating that increased impulsivity and intolerance of delayed reward are part of the psychopathology of binge-eating. Lisdexamfetamine (0.8 mg/kg, orally ( d-amphetamine base)) reversed the reduced preference of binge-eating rats for larger rewards at delay intervals of 4 s, 8 s and 32 s and across all sessions. Lisdexamfetamine-treated binge-eating rats consumed the same number of pellets as vehicle-treated, binge-eating rats and non-binge-eating controls eliminating the possibility lisdexamfetamine's actions on appetite or satiety mediated its effects on operant responding for food pellets in delay-discounting. In summary, binge-eating rats showed increased impulsive choice compared with non-binge-eating controls that was reversed by lisdexamfetamine, complementing results showing lisdexamfetamine reduced impulsiveness scores in patients with binge-eating disorder.
authors.affiliation: 1 RenaSci Ltd, BioCity, Nottingham, UK.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Vickers
authors.affiliation: 1 RenaSci Ltd, BioCity, Nottingham, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Goddard
authors.affiliation: 1 RenaSci Ltd, BioCity, Nottingham, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brammer
authors.affiliation: 2 Shire Development Inc., Lexington, MA, USA.|Current address: Teva Pharmaceuticals, 145 Brandywine Parkway, West Chester, PA 19380, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.affiliation: 1 RenaSci Ltd, BioCity, Nottingham, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
mesh_terms: D000818:Animals; D002032:Bulimia / Q000188:drug therapy*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D005260:Female; D005502:Food; D007175:Impulsive Behavior / Q000187:drug effects*; D000069478:Lisdexamfetamine Dimesylate / Q000494:pharmacology*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D011355:Prodrugs; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine
keywords: Lisdexamfetamine; binge-eating; delay-discounting; impulsivity