Involvement of endogenous opioid peptides in fenfluramine anorexia

The effect of chronic fenfluramine (20 mg/kg, once daily) injections on the brain and peripheral immunoreactive (ir) dynorphin (DYN), alpha-neoendorphin (ANEO) and beta-endorphin (BE) was studied in rats. Fenfluramine injected repeatedly for 5 and 9 days induced anorexia. In the same animals there were no significant changes in the ir-DYN and ir-ANEO contents in the brain and pituitary. However, the ir-DYN and ir-ANEO contents in the gastrointestinal tract (duodenum) were markedly decreased after 5 and 9 days of fenfluramine injection. In contrast to ir-DYN and ir-ANEO, there was an increase in the hypothalamic and a decrease in the anterior lobe of pituitary ir-BE content. There was no significant change in the neurointermediate (NI) lobe of the pituitary. The results of our study suggest that part of the fenfluramine anorexia may be mediated by the peripheral prodynorphin and central beta-endorphin systems.