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 2hr 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 (3.0–30mg/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.