Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorophenylalanine

Science  23 Apr 1976:
Vol. 192, Issue 4237, pp. 382-385
DOI: 10.1126/science.130678


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.