Gabapentin increases aminooxyacetic acid-induced GABA accumulation in several regions of rat brain.
Gabapentin exerts anticonvulsant effects in different animal models of seizure states and in epileptic patients with different seizure types, but the mechanism of action of these effects is unknown. In the present study, the gamma-aminobutyric acid (GABA) accumulation induced by aminooxyacetic acid (AOAA) was used as a method to study the effects of gabapentin on regional turnover of GABA in the rat brain. Gabapentin was administered at a dose of 23 mg/kg i.p. (the ED95 against tonic electroconvulsions in rats) 1, 2 and 8 h prior to injection of AOAA, 100 mg/kg, i.p. Gabapentin significantly increased the AOAA-induced GABA accumulation in most of the 12 brain regions examined, but the time course of the increases in GABA accumulation differed from region to region. Regions in which the time course of the increase in GABA accumulation was similar to the anticonvulsant time course of gabapentin included substantia nigra, amygdala and thalamus. The data suggest that an effect of gabapentin on GABA synthesis might be involved in its mechanism of anticonvulsant action.
Löscher
W
W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, F.R.G.
Hönack
D
D
Taylor
C P
CP
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids; D004597:Electroshock; D005260:Female; D000077206:Gabapentin; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000517:prevention & control; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin