Acute effects of gamma-vinyl GABA (vigabatrin) on hippocampal GABAergic inhibition in vitro.
The acute effects of gamma-vinyl-GABA (GVG) on GABAergic inhibition were investigated in the hippocampal slice preparation using the paired-pulse test of inhibition during extracellular recordings. Superfusion of GVG (100-500 microM) for 60 min resulted in a concentration-dependent decrease in GABAergic inhibition. Slices superfused with higher concentrations of GVG (0.5-1 mM) were hyperexcitable as demonstrated by the appearance of multiple spikes. Binding studies showed that GVG (1 mM) had no effect on the binding of [3H]flunitrazepam or [3H]TBOB and displaced no more than 15% of specific [3H]GABA binding, which indicates that GVG-induced disinhibition is not mediated through an action at the GABAA receptor complex. Consistent with this suggestion is the finding that GVG (500 microM) had little effect on the inhibition of the orthodromically evoked CA1 population spike produced by the GABAA receptor agonist muscimol (10 microM), whereas this inhibition was considerably attenuated by the GABAA receptor antagonist, bicuculline methiodide (5 microM). The results of this study suggest that the acute actions of GVG on the GABAergic neurotransmitter system are not involved in its anticonvulsant effect.
Jackson
M F
MF
Department of Pharmacology and Therapeutics, McGill University, Montreal, Que., Canada.
Dennis
T
T
Esplin
B
B
Capek
R
R
D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D018756:GABA Antagonists; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin