Microdialysis monitoring of variations in extracellular levels of serotonin, GABA and excitatory amino acids in the frontal cortex of awake rats 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), excitatory (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 these neurotransmitters were measured with HPLC coupled to electrochemical detection or with capillary electrophoresis coupled to laser-induced fluoresence detection (CE-LIFD). In a first study, single intraperitoneal administration of D-fen (0.5, 1.3, 5 and 10 mg/kg) increased extracellular 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 microliters/min in 30 microliters of perfusion fluid for 20 min, 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 magnitude of the changes induced by systemic administration or local infusion of D-fen on frontocortical extracellular levels of several neurotransmitters (5-HT > > Asp > GABA = Glu) demonstrate that D-fen, an indirect serotoninergic agonist, mainly increases 5-HT release while producing slight (Asp) or no (Glu, GABA) short-term in vivo variations in amino acid extracellular levels in the rat frontal cortex.
Rocher
C
C
Faculté de Pharmacie, Laboratoire de Pharmacologie, Châtenay-Malabry, France.
Bert
L
L
Robert
F
F
Trouvin
J H
JH
Renaud
B
B
Jacquot
C
C
Gardier
A M
AM
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D019075:Electrophoresis, Capillary; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007834:Lasers; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018846:Excitatory Amino Acids; D005456:Fluorescent Dyes; D018490:Serotonin Agents; D005277:Fenfluramine; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid