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.

Food Addiction and Binge Eating: Lessons Learned from Animal Models

“…Oral lisdexamfetamine dimesylate (LDX), a prodrug of dextroamfetamine, is currently the only drug to be approved in the USA for the treatment of moderate to severe BED in adult patients [ 225 ]. When given acutely in a female rat BED model, LDX attenuated binge-eating of chocolate without influencing the consumption of normal chow or affecting the bodyweight of the animals [ 226 ] and reduced impulsiveness and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model [ 227 , 228 ]. Pharmacological characterisation indicated that LDX attenuates binge-eating in part by indirect activation of α1-adrenergic and possibly also dopamine D1 receptors in the CNS, but α2-adrenergic and D2 receptors are not involved [ 226 ].…”

Machine Learning Based Classification of Deep Brain Stimulation Outcomes in a Rat Model of Binge Eating Using Ventral Striatal Oscillations

“…This “binge-like” feeding has been shown to result in more significant weight gain than was observed with continuous access to the same diet—as is used in models of diet-induced obesity ( 20 ). Prior work has also demonstrated that chronic, irregular, limited access to palatable food can result in compulsive feeding behavior ( 21 , 22 ) and increased impulsivity ( 23 ). Palatable sweet-fat and regular house chow consumption were measured during all limited access sessions.…”

“…In this study, we used an established rat model of binge eating to produce binge-like feeding behavior ( 18 – 20 ). Similar rodent models of binge eating have resulted in weight gain ( 20 ), compulsive feeding behavior ( 21 , 22 ) and increased impulsivity ( 23 ) thus displaying traits commonly observed in appetitive disorders like substance use and binge eating disorder. It is important to acknowledge, however, that this is a pre-clinical approximation of the clinical condition, and many successful pharmacologic trials using this rodent/rat model have failed to translate clinically with the exception of lisdexamfetamine ( 24 , 25 ).…”

Machine learning based classification of deep brain stimulation outcomes in a rat model of binge eating using ventral striatal oscillations

“…This “binge-like” feeding has been shown to result in more significant weight gain than is observed with continuous access to the same diet -- as is used in models of diet-induced obesity [18]. Prior work has also demonstrated that chronic, irregular, limited access to palatable food can result in compulsive feeding behavior[21, 22] and increased impulsivity [23]. Palatable sweet-fat and regular house chow consumption was measured during all limited access sessions.…”

“…In this study, we used an established rat model of binge eating to produce binge-like feeding behavior [18–20], Similar rodent models of binge eating have resulted in weight gain[18], compulsive feeding behavior[21, 22] and increased impulsivity[23] thus displaying problems in overlapping psychological domains to patients with binge eating disorder. It is important to acknowledge however, that this is merely a pre-clinical approximation of the clinical condition and many successful pharmacologic trials using this rodent/rat model have failed to translate clinically with the exception of lisdexamfetamine [24, 25].…”