MICRODIALYSIS MONITORING OF VARIATIONS IN EXTRACELLULAR LEVELS OF SEROTONIN, GABA AND EXCITATORY AMINO-ACIDS IN THE FRONTAL-CORTEX OF AWAKERATS IN RESPONSE TO A SINGLE PERIPHERAL OR CENTRAL ADMINISTRATION OF DEXFENFLURAMINE

The effects of a single dexfenfluramine (D-fen) administration on the release of endogenous serotonin (5-hydroxytryptamine, 5-HT), excitator y (glutamate, Glu, aspartate, Asp) and inhibitory (gamma-aminobutyric acid, GABA) amino acids from the frontal cortex were studied by using in vivo microdialysis in freely-moving rats. Extracellular levels of t hese neurotransmitters were measured with HPLC coupled to electrochemi cal detection or with capillary electrophoresis coupled to laser-induc ed fluorescence detection (CE-LIFD). In a first study, single intraper itoneal administration of D-fen (0.5, 1.3, 5 and 10 mg/kg) increased e xtracellular 5-HT levels in a dose-dependent manner (maximal increase by 982% over baseline for the highest dose) while changes in Glu, Asp or GABA never reached statistical significance. In a second study, 73 nM of D-fen applied locally through the frontocortical dialysis probe, at a flow rate of 1.5 mu l/min in 30 mu l of perfusion fluid for 20 m in, increased extracellular 5-HT and Asp levels [the maximal increases were to 1804% and 280% of the respective basal values (100%)] without altering extracellular levels of Glu and GABA. Thus, the order of mag nitude of the changes induced by systemic administration or local infu sion of D-fen on frontocortical extracellular levels of several neurot ransmitters (5-HT >> Asp > GABA = Glu) demonstrate that D-fen, an indi rect serotoninergic agonist, mainly increases 5-HT release while produ cing slight (Asp) or no (Glu, GABA) short-term in vivo variations in a mino acid extracellular levels in the rat frontal cortex.