The effect of diazepam on the cerebral metabolic state in rats and its interaction with nitrous oxide.

Abstract

It has previously been shown in rats that diazepam alone has no effect on the cerebral metabolic rate (CMRO2) but that it interacts with nitrous oxide to produce a 40 per cent reduction in the CMRO2 value. In the present study, the effect of sedative doses of diazepam on the cerebral energy state, glycolysis, citric acid cycle, and amino acid metabolism in rats was determined in the presence and absence of a simultaneous administration of 70 per cent nitrous oxide, 45 s to 30 min after the diazepam injection. The metabolic response was very similar in the two groups despite the differences in metabolic rates of oxygen consumption. There were no changes in the cortical concentrations in ATP, ADP, AMP, phosphocreatine and creatine. The brain glycogen concentration was elevated during diazepam sedation, whereas brain glucose levels remained close to normal values except at 30 min after administration of diazepam alone, when the glucose level showed a 30 per cent increase. The onset of diazepam sedation was associated with an inhibition of glycolysis at the phosphofructokinase step in both groups. The reduced pyruvate concentration subsequently leads to a reduction in the pool size of the citric acid cycle intermediates. The concentrations of alanine and glutamate decreased during the period of diazepam sedation, while those of aspartate and glutamine increased. GABA and ammonia concentrations remained unchanged. Based on the cerebral metabolic response, the onset of diazepam sedation appears to be associated with an inhibition of rate of metabolism (glycolysis), both in the presence and absence of nitrous oxide. In that respect, diazepam has a metabolic profile similar to barbiturates.