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.
Rocher
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Laboratoire de Neuropharmacologie UPRES EAD MENRT, Faculté de Pharmacie IFR-ISIT, Institut de Signalisation et Innovation Thérapeutique, Université Paris-Sud, Châtenay-Malabry, France.
Gardier
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AM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology*
D018490:Serotonin Agents; D013566:Sympathomimetics; D005277:Fenfluramine; D012701:Serotonin; D018698:Glutamic Acid; D008694:Methamphetamine