Elevation of brain GABA concentrations with amino-oxyacetic acid; effect on the hyperactivity syndrome produced by increased 5-hydroxytryptamine synthesis in rats.
Pretreatment of rats with aminooxyacetic acid (AOAA; 40 mg/kg) raised the concentration of rat brain GABA and inhibited the hyperactivity produced by increasing brain 5-hydroxytryptamine (5-HT) concentration by administration of tranylcypromine and L-tryptophan. The maximum effect was seen 90 min after AOAA injection with smaller effects 30 and 180 min after injection. AOAA did not affect the rate of 5-HT accumulation in the brain, but did inhibit the hyperactivity response which follows injection of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine, suggesting that post-synaptic 5-HT responses were being inhibited. AOAA also inhibited the locomotor activity which follows administration of tranylcypromine and L-dopa. Blockade of GABA receptors by injection of picrotoxin (2.5 mg/kg) enhanced the dopamine hyperactivity. Since a dopaminergic system has been shown to be involved in the 5-HT hyperactivity syndrome and appears to act post-synaptically to the 5-HT neurones initiating the syndrome it is suggested that inhibition of the 5-HT hyperactivity syndrome may be due to accumulation of GABA distal to the dopaminergic receptors.
D000085:Acetates / Q000494:pharmacology*; D000613:Aminobutyrates / Q000378:metabolism*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis*; D013577:Syndrome; D014191:Tranylcypromine / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D000613:Aminobutyrates; D000625:Aminooxyacetic Acid; D004298:Dopamine; D009638:Norepinephrine; D010852:Picrotoxin; D012701:Serotonin; D014191:Tranylcypromine; D014364:Tryptophan; D005680:gamma-Aminobutyric Acid