Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine.

Loss of brain serotonin was associated with overeating and increased body weight. Rats injected with p-chlorophenylalanine intraventricularly began overeating after 3 days and continued to display marked hyperphagia, primarily in the daytime, accompanied by increased body weight for 1 to 2 weeks. The effect was related to drug dose and to the degree and duration of serotonin depletion. Norepinephrine and dopamine levels were not significantly affected. It is concluded that p-chlorophenylalanine disinhibits feeding, as it does a number of other behaviors, by depleting serotonin. This suggests that hypothalamic lesions or dietary deficiencies which selectively and sufficiently deplete serotonin would lead to overeating.