The Effect of Pronounced Hypoglycemia on Monoamine Metabolism in Rat Brain

Abstract

The cerebral metabolism of catechol and indole amines was studied in paralyzed and lightly anesthetized (70% N2O) rats in which severe hypoglycemia was induced by insulin. When blood glucose concentrations fell towards 1 μmol·g−1 and the electrocorticogram (EEG) showed high-amplitude slow waves with interspersed polysplkes, the tissue contents of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were reduced. The rate of hydroxylation of tyrosine, measured as accumulation of dihydroxyphenylalanine (dopa) following inhibition of aromatic L-amino acid decarboxylase with NSD 1015, rose in cortex and striatum, while tryptophan hydroxylation increased moderately in cortical tissue. Aggravation of the hypoglycemia with cessation of spontaneous EEG activity was accompanied by progressive reduction in tissue contents of DA, NE, and 5-HT and by accumulation of 5-hydroxyindole acetic acid (5-HIAA). In this period, tyrosine hydroxylation rate was reduced in limbic areas and in striatum, but not in the cortex, while tryptophan hydroxylation was reduced in limbic areas only. When recovery was induced for 45 min by i.v. glucose following 30 min recording of isoelectric EEG, there was extensive recovery of tissue concentrations of DA and 5-HT but incomplete recovery of NE concentrations. Tyrosine hydroxylation rate was increased in all areas, but tryptophan hydroxylation either remained at control levels (striatum and cortex) or fell (limbic area). It is concluded that severe hypoglycemia leads to a gross derangement of brain monoamine metabolism, which seems to include an increase in NE turnover during both the precomatose phase and the recovery phase.