title: The effects of sodium valproate on gamma-aminobutyrate metabolism and behaviour in naive and ethanolamine-O-sulphate pretreated rats and mice.
abstract: Sodium valproate was injected acutely (400 mg/kg i.p.) into naive and ethanoloamine-O-sulphate chronically pretreated rats and mice, in an attempt to gain further insight into the effects of this anticonvulsant on GABA metabolism. Sodium valproate significantly enhanced the activity of GAD in the medulla and pons, cerebellum and midbrain regions of rats, and partially relieved the suppression of GAD activity caused by chronic GABA-transaminase inhibition in whole mouse brain. In combination with EOS, sodium valproate caused behavioural excitation in mice which was similar to that sometimes seen with high doses of some GABA-T inhibitors. Pretreatment with EOS potentiated the characteristic abstinence behaviour caused by sodium valproate in rats, though no further significant rise in cerebral GABA levels was observed. In view of the neuronal location of GAD, the elevation of cerebral GABA levels at least in part by potentiation of GAD activity could be involved in the mediation of the anticonvulsant activity of sodium valproate.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D004983:Ethanolamines; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; C020619:ethanolamine O-sulfate