The significance of extracellular GABA in the substantia nigra of the rat during seizures and anticonvulsant treatments.
The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold increase in the extracellular content of GABA. This increase lasted for at least 72 h. PTZ-induced convulsions were partly antagonized by the GVG treatment. The increase of extracellular GABA after gamma-vinyl-GABA was not affected by infusion of tetrodotoxin. In contrast valproic acid (200 mg/kg), although effective in preventing pentylenetetrazol (PTZ)-induced convulsions, did not affect extracellular GABA in the SNR. PTZ-induced convulsions did not modify extracellular GABA, neither in control rats nor in valproic acid or gamma-vinyl-GABA pretreated animals. The results do not support the idea that extracellular GABA in the SNR plays a significant role in anti-convulsive treatment. However, the present data can also be interpreted that extracellular GABA, as sampled by microdialysis, is not a reliable marker for GABA release.
Sayin
U
U
DETAM, Istanbul Faculty of Medicine, Capa, Turkey.
Timmerman
W
W
Westerink
B H
BH
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017551:Microdialysis; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013378:Substantia Nigra / Q000737:chemistry*; D014635:Valproic Acid / Q000494:pharmacology; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D020888:Vigabatrin; D010433:Pentylenetetrazole