Effects of gamma-butyrolactone on local cerebral glucose utilization in the rat.

Abstract

Abstract— The effects of graded doses of γ‐butyrolactone on the rates of glucose utilization in 29 structural components of the albino rat brain were studied by means of the [14C]deoxyglucose technique. The γ‐butyrolactone in doses of 75, 150, 300, and 600 mg/kg of body weight was administered intravenously in divided doses, two‐thirds 45min and one‐third 15min before the administration of the pulse of [14C]deoxyglucose. Electroencephalographic recordings were carried out in some of the rats administered each of the above doses. The results demonstrate dose‐dependent changes in the level of consciousness, electroencephalographic activity, and the rates of local cerebral glucose utilization. At the two lower doses there were no notable effects on behavior, but there was significant slowing of the electroencephalogram. The higher doses caused a trance‐like state associated with long periods of electroencephalographic silence punctuated by bursts of polyspike and wave activity. At all doses there was significant depression of the rates of cerebral glucose utilization throughout the brain, the greater the dose the greater the magnitude of the depression. The effects were greater in gray structures than in white matter. At the maximum doses local cerebral glucose utilization was profoundly depressed to mean values of 32% and 58% of control values in gray and white matter, respectively. There was no apparent selectivity or specificity in the effects of γ‐butyrolactone on glucose utilization in the various gray structures of the brain; all 26 gray structures studied exhibited similar dose‐response relationships. Animals similarly treated with γ‐butyrolactone and left undisturbed regained completely normal behavior and electroencephalographic activity in several hours. These results suggest that γ‐butyrolactone profoundly depresses cerebral energy metabolism throughout the brain and that it might prove useful in clinical conditions in which a temporary reversible reduction in cerebral energy demand is desired.