Neuronal activity, amino acid concentration and amino acid release in the substantia nigra of the rat after sodium valproate.
The effects of sodium valproate on extracellularly recorded spontaneous neuronal activity and striatal-evoked inhibition in the substantia nigra zona reticulata of the rat were compared with its effects on the tissue concentration of endogenous amino acids and their spontaneous release into perfusates of this region obtained with a push-pull cannula. Valproate (200 mg/kg i.p.) produced a rapid and sustained reduction in the firing rate of all reticulata neurones tested and a concomitant increase in the duration of striatal-evoked inhibition. No change in the spontaneous release of any amino acid was observed. A significant elevation of nigral gamma-aminobutyric acid concentration was seen in both anaesthetized and non-anaesthetized animals, but this occurred only after 60 minutes. Valproate produced a rapid decline in nigral aspartate in non-anaesthetized but not in anaesthetized animals. The results of this study suggest that the acute depressant effect of valproate is unrelated to its ability to alter the concentration of GABA or aspartate in brain and is most likely due to a postsynaptic action.
Farrant
M
M
Department of Pharmacology, University College London, U.K.
Webster
R A
RA
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid