Monoamine metabolism during bicuculline-induced epileptic seizures in the rat

Abstract

Brain levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 30, 60 and 120 min of sustained seizure activity, induced in paralyzed, artificially ventilated and anaesthetized (70% N2O) rats by administration of bicuculline (1.2 mg/kg i.v.). In separate animals the rates of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) were estimated in three different brain regions after blockage of the aromatic L-amino acid decarboxylase with NSD 1015 (100 mg/kg). The tissue level of NA was markedly reduced at 30 min and remained low during 120 min of sustained epileptic seizures. In contrast, the DA concentration, being essentially unaffected at 30 min, continuously increased during the following 90 min. 5-HT decreased significantly after 30 min but returned to control levels following 60 and 120 min of seizure activity. The 5-HIAA concentration progressively increased. In all three brain regions (striatum, limbic forebrain and hemispheres) the rate of tyrosine hydroxylation increased. Tryptophan hydroxylation showed a significant increase only in the limbic forebrain. The results suggest that bicuculline-induced seizures lead to an increased functional activity in NA neurons and, at least initially, also in 5-HT neurons. In contrast, DA neurons appear to be inhibited.