Amphetamine-induced hyperphagia and obesity caused by intraventricular or lateral hypothalamic injections in rats

Overeating and obesity relative to controls was produced by multiple bilateral injections of 0.5 mg of amphetamine in the lateral ventricles of female rats eating a palatable, high fat diet. This behavioral and physiological rebound following the expected period of anorexia was accompanied by long-term depletion of dopamine in the striatum and of norepinephrine in the hypothalamus. This suggested the next experiment in which 50 micrograms of amphetamine were injected repeatedly in the lateral hypothalamus; again a brief period of anorexia was followed by hyperphagia and chronic obesity. This suggests that amphetamine acts in the lateral hypothalamus not only to suppress feeding, but in high doses it may also have local neurotoxic effects that cause an upward shift in body weight maintained by overeating.