Effects of repeated systemic administration of d-Fenfluramine on serotonin and glutamate release in rat ventral hippocampus: comparison with methamphetamine using in vivo microdialysis.

We compared the effects of three systemic injections of various doses of d-Fenfluramine, an indirect serotonergic agonist (1.3, 5 or 10 mg/kg), to those of a known neurotoxin, methamphetamine (METH, at a 7.5 mg/kg dose), given i.p. at 2-h intervals, simultaneously on extracellular levels of glutamate [Gluext] and 5-HT [5-HText] in the ventral hippocampus (VHPC) using in vivo microdialysis in conscious rats. METH markedly increased both [Gluext] (+77% over the control value in saline-treated rats) and [5-HText] (around +250% over controls) in the VHPC. d-Fenfluramine, at all the doses studied, induced gradual increases of [5-HText] in the VHPC (between +125% and +417% over control values), but did not modify [Gluext]. These data highlight marked in vivo differences between METH and d-Fenfluramine in their effects on extracellular levels of 5-HT and Glu in the rat ventral hippocampus following their repeated systemic administration.