Effects of fenfluramine and phentermine (fen-phen) on dopamine and serotonin release in rat striatum: in vivo microdialysis study in conscious animals

Abstract

We measured the effects of acute or chronic administration of fenfluramine and phentermine, alone or in combination, on brain dopamine and serotonin release into striatal dialysates of freely moving rats. Samples collected every 30 min were assayed in a single run by high-pressure liquid chromatography. Acute or chronic administration of fenfluramine (1 mg/kg, i.p.) did not significantly change dopamine concentrations in rat striatal dialysates, but increased those of serotonin by 182% (acute) and 124% (chronic). Phentermine (2 mg/kg, i.p.), on the other hand, significantly increased dopamine concentrations by 52% (acute) and 80% (chronic) without affecting those of serotonin. Administration of the drugs in combination (fenfluramine 1 mg/kg and phentermine 2 mg/kg) amplified the effects of each, increasing striatal dopamine concentrations by 209% (acute) and serotonin concentrations by 330% (acute) and 299% (chronic).