Elevation of brain GABA concentrations with amino-oxyacetic acid; effect on the hyperactivity syndrome produced by increased 5-hydroxytryptamine synthesis in rats.

Abstract

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.