COMPARISON OF THE EFFECTS OF GAMMA-HYDROXYBUTYRATE AND GAMMA-BUTYROLACTONE ON CEREBRAL CARBOHYDRATE-METABOLISM

The metabolic effects of 60-min exposure to 250-2000 mg γ-hydroxybutyrate (GHB) per kilogram or 150-1200 mg γ-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Kreb's cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, α-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivations of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.