Cerebral metabolism of glucose in adrenalectomized rats: effect of treatment with l-DOPA and a monoamine oxidase inhibitor

Abstract

The brain is unique among tissues in that it is almost entirely dependent on glucose as its source of energy and in that it metabolizes glucose rapidly to those amino acids (glutamate, glutamine, GABA and aspartate) that are in equilibrium with the tricarboxylic acid cycle intermediates. This reaction is so rapid that as early as 5 min after [14C]glucose injection these 14C-labeled amino acids are by far the most abundant metabolites of glucose in brain 5. Treatment of control rats with L-DOPA and an inhibitor (fl-phenylisopropylhydrazine, JB 516) of monoamine oxidase was found to inhibit this cerebral metabolism of glucose and to cause increases in the concentrations of glucose in plasma and in brain 4. We now report studies of the effects of administration of L-DOPA and JB 516 to adrenalectomized rats. Male Sprague-Dawley rats weighing 265-365 g were used. Bilaterally adrenalectomized rats were obtained from A. R. Schmidt Co., Madison, Wisc. These were allowed free access to solid food, and their drinking water was a mixture of 5 ~ glucose in 0.9 ~o saline. Control animals were fed ad libitum. [U-14C]Glucose (20/zCi, 0.24 mg in 0.2 ml) was injected intravenously to unanesthetized control and adrenalectomized rats; 5 of the adrenalectomized rats had been injected with JB 516 (20 mg/kg, i.p., 2.25 h earlier) and with L-DOPA (100 mg/kg, i.v., 15 min earlier). Small samples of blood were collected from the femoral artery at intervals after the glucose injection. At 14.5 rain after glucose injection, the rats were injected with sodium pentobarbital (20 mg), and 30 sec later the rats were dropped head first into liquid nitrogen and the brains were frozen in situ. The frozen brains were then chiselled out for chemical analysis. The methods used for chemical determinations and measurements of radioactivity have been described in detail 4. The specific activity of glucose in plasma was determined by dividing total 14C in plasma by the concentration of glucose determined enzymatically4.This simplified method was used because it has been shown in rats that over 96 ~ of total 14C in blood remains as [14C]glucose for as long as 15 min after injection of [U-14C]