BICUCULLINE METHIODIDE INFLUENCES THE CENTRAL-NERVOUS-SYSTEM TO PRODUCE HYPERGLYCEMIA IN RATS

The influence of bicuculline methiodide (BMI), a gamma-aminobutyric ac id (GABA) receptor antagonist, on central nervous system regulation of blood glucose homeostasis was studied in fed rats. Injection of BMI ( 1-10 nmol) into the third ventricle was found to produce hepatic Venou s hyperglycemia in a dose-dependent manner. This change was associated with increased secretion of epinephrine and glucagon. The role of epi nephrine in hyperglycemia was then studied in bilaterally adrenalectom ized (ADX) rats injected with BMI. Plasma glucose concentration was fo und to increase in ADX rats although the level was approximately half that for intact rats and significantly higher than for controls. The i ncrease in epinephrine and glucagon secretion seen in intact rats, but not in ADX rats, suggests BMI-induced epinephrine release is responsi ble for the glucagon secretion. Three possible mechanisms are suggeste d to account for the rise in plasma glucose in the hepatic vein after injection of BMI: 1) that epinephrine is secreted by the adrenal medul la, 2) that epinephrine secretion stimulates glucagon secretion or 3) that there may be some direct innervation of the liver in rats.