Acute effects of gamma-vinyl GABA on the GABAergic system in rats as studied by microdialysis.
The acute effects of the irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor, gamma-vinyl GABA (Vigabatrin), were studied in the central nervous system of the rat. GABA concentrations were monitored in the hippocampus by implantation of microdialysis probes. Two doses of gamma-vinyl GABA (1.6 and 8.0 mM) were administered via the probes and were found to cause a transient increase in the basal GABA outflow (10-fold) during the period of drug administration. In addition, gamma-vinyl GABA pretreatment (1.6 mM) seemed to decrease K(+)-evoked GABA release (P < 0.05). The immediate increase of GABA outflow after gamma-vinyl GABA administration may be the result of direct blockade of GABA uptake sites, a finding which further indicates that the action of GABA transaminase inhibitors may be mediated partly through GABA uptake inhibition.
Jolkkonen
J
J
Department of Neurology and Pathology, University of Kuopio, Finland.
Mazurkiewicz
M
M
Lahtinen
H
H
Riekkinen
P
P
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000614:Aminocaproates; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin