Lisdexamfetamine reduces the compulsive and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model

• Published in: Journal of psychopharmacology (Oxford) Vol. 30; no. 7; pp. 662 - 675
• Main Authors: Heal, David J, Goddard, Simon, Brammer, Richard J, Hutson, Peter H, Vickers, Steven P
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2016
• Subjects: Animals; Binge-Eating Disorder - drug therapy; Bulimia - drug therapy; Compulsive Behavior - drug therapy; Conditioning, Operant - drug effects; Feeding Behavior - drug effects; Female; Lisdexamfetamine Dimesylate - pharmacology; Rats; Rats, Wistar; Reward; compulsive; Lisdexamfetamine; perseverative; conflict model; binge eating
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881116647506

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.