Acute fenfluramine administration reduces neuropeptide Y concentrations in specific hypothalamic regions of the rat: possible implications for the anorectic effect of fenfluramine.

Neuropeptide Y (NPY), a powerful central appetite stimulant, coexists in several hypothalamic areas with serotonin, which suppresses feeding. This study investigated the effect of acute administration of the serotonergic drug, fenfluramine, on NPY concentrations in microdissected hypothalamic nuclei. Adult male Wistar rats were given fenfluramine (10 mg/kg, n = 7) or saline (n = 7), intraperitoneally 1 h before darkness. Food was presented immediately before darkness and the rats were killed during the first 4 h of darkness. Fenfluramine injection significantly reduced food intake. In fenfluramine-injected animals, NPY levels in the ventromedial and dorsomedial nuclei and in the lateral hypothalamic and lateral preoptic areas were significantly lower than in saline-injected controls. The ventromedial and dorsomedial nuclei and the lateral hypothalamic area are sites which mediate the hyperphagic action of centrally injected NPY. Selective NPY changes in specific nuclei after fenfluramine injection suggest functional interaction between NPYergic and serotonergic systems, and may indicate that NPY is involved in mediating the anorectic effect of serotonergic agents.