title: Effects of lisdexamfetamine in a rat model of binge-eating.
abstract: Binge-eating disorder is a common psychiatric disorder affecting ~2% of adults. Binge-eating was initiated in freely-fed, lean, adult, female rats by giving unpredictable, intermittent access to ground, milk chocolate over four weeks. The rats avidly consumed chocolate during 2 hr binge sessions, with compensatory reductions of normal chow intake in these sessions and the days thereafter. Bodyweights of binge-eating rats were normal. The model's predictive validity was explored using nalmefene (0.1-1.0mg/kg), R-baclofen (1.0-10mg/kg) and SB-334867 (3.0-30 mg/kg) (orexin-1 antagonist), which all selectively decreased chocolate bingeing without reducing chow intake. Sibutramine (0.3-5.0mg/kg) non-selectively reduced chocolate and chow consumption. Olanzapine (0.3-3.0mg/kg) was without effect and rolipram (1.0-10mg/kg) abolished all ingestive behaviour. The pro-drug, lisdexamfetamine (LDX; 0.1-1.5mg/kg), dose-dependently reduced chocolate bingeing by ⩽ 71% without significantly decreasing normal chow intake. Its metabolite, D-amphetamine (0.1-1.0mg/kg), dose-dependently and preferentially decreased chocolate bingeing ⩽ 56%. Using selective antagonists to characterize LDX's actions revealed the reduction of chocolate bingeing was partially blocked by prazosin (α1-adrenoceptor; 0.3 and 1.0mg/kg) and possibly by SCH-23390 (D1; 0.1mg/kg). RX821002 (α2-adrenoceptor; 0.1 and 0.3mg/kg) and raclopride (D2; 0.3 and 0.5mg/kg) were without effect. The results indicate that LDX, via its metabolite, d-amphetamine, reduces chocolate bingeing, partly by indirect activation of α1-adrenoceptors and perhaps D1 receptors.
authors.affiliation: RenaSci Ltd, BioCity, Nottingham, UK.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Vickers
authors.affiliation: Shire Pharmaceuticals Ltd, Basingstoke, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hackett
authors.affiliation: Shire Pharmaceuticals Ltd, Basingstoke, UK.
authors.forename: Fraser
authors.initials: F
authors.lastname: Murray
authors.affiliation: Shire Development Inc, Wayne, PA, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.affiliation: RenaSci Ltd, BioCity, Nottingham, UK david.heal@renasci.co.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002032:Bulimia / Q000188:drug therapy*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D000069478:Lisdexamfetamine Dimesylate / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077152:Olanzapine; D011224:Prazosin / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D011355:Prodrugs; C534628:SCH 23390; D001569:Benzodiazepines; D020891:Raclopride; D009271:Naltrexone; C058525:2-methoxyidazoxan; D001418:Baclofen; D020889:Rolipram; D000077152:Olanzapine; D000069478:Lisdexamfetamine Dimesylate; C038981:nalmefene; D011224:Prazosin; D019329:Idazoxan
keywords: Lisdexamfetamine; binge-eating; binge-eating disorder; d-amphetamine; rats