Amphetamine Dose-Dependently Decreases and Increases Binge Intake of Fat and Sucrose Independent of Sex.

Abstract

Amphetamine was formerly used as a treatment to combat obesity, but amphetamine's use as an appetite suppressant was discontinued because of its significant abuse potential. Most of the rewarding and reinforcing effects of amphetamine differ by sex, with females showing higher levels of drug intake and amphetamine-induced motivation, relapse, and locomotion, but it is unknownwhether amphetamine's effects on feeding also differ by sex. Furthermore, previous research on the anorectic effects of amphetamine has been focused primarily on its effects on baseline homeostatic feeding, but it is unknown whether amphetamine also affects hedonic, reward-related feeding, which is an important factor driving the rise in obesity levels. This studytested whether amphetamine alters food intake in a sex-dependent manner in two reward-related feeding paradigms: a sucrose two-bottle choice test and a high-fat/high-sugar binge intake model. Amphetamine altered food intake equally in males and females in both paradigms, with higher doses significantly inhibiting feeding and low doses of amphetamine increasing feeding at later time points. Amphetamine's effects on feeding and drug reward may be mediated by distinct mechanisms, which could allow for the development of new approaches to combat obesity with limited abuse and addiction-related side effects.