Date of Completion
John Salamone; Anastasios Tzingounis
Physiology and Neurobiology
Tetrabenazine (TBZ), a vesicular monoamine transporter-2 (VMAT-2) inhibitor that preferentially depletes dopamine (DA), produces depressive symptoms including motivational symptoms in humans. In rodents, it reduces selection of high-effort effort alternatives in effort-based choice tasks, but does not affect food intake or preference (Nunes et al. 2013; Yang et al. 2020). However, no studies have focused on the effects of TBZ on binge-like eating to determine if it would influence “hedonic eating”. The current study used both binge-like eating and effort-based operant tasks in rats. To assess effects on binge-like eating, non-food restricted rats (n=8) were exposed to chocolate over 12 sessions and their chocolate intake was recorded. Following the initial training, rats were tested for the effects of either vehicle or 1.0 mg/kg TBZ. There was no significant effect of 1.0 mg/kg TBZ treatment on chocolate intake. For the effects on operant behavior, food-restricted rats (n=8) were trained on a fixed-ratio (FR)5/chow feeding choice task. With this task, animals have a choice between lever pressing to obtain a relatively preferred food (Bioserve pellets) or consuming a less preferred food (lab chow) that is available in the chamber. After training, rats were tested for the effects of injections of vehicle or 1.0 mg/kg TBZ. Administration of TBZ shifted the behavior from lever pressing, the high-effort alternative, to chow intake. Unlike high-effort choice, binge-like eating behavior was not affected by the depletion of DA induced by TBZ. These results indicate that TBZ is not impairing “hedonic eating” at the dose that reduces selection of high-effort activities such as lever pressing, further validating the TBZ model of motivational dysfunction.
Fleeher, Reileigh, "The Influence of Tetrabenazine on Operant Behavior and Binge-Like Eating Model in Rats" (2022). Honors Scholar Theses. 899.