Determination of striatal extracellular gamma-aminobutyric acid in non-hibernating and hibernating Arctic ground squirrels using quantitative microdialysis

This study determined extracellular concentrations of gamma-aminobutyric ac id ([GABA](ecf)) in striatum of non-hibernating and hibernating arctic grou nd squirrels to test the hypothesis that an increase in [GABA](ecf) was ass ociated with profound CNS depression during hibernation. Quantitative micro dialysis procedures were employed to circumvent the effects of low temperat ure on the relative recovery of the analyte across the dialysis membrane an d yielded for the first time quantitative in vivo estimates of [GABA](ecf) in any brain region or any species. Laboratory housed, wild caught Arctic g round squirrels (Spermophilus parryii) were implanted intraperitoneally wit h radio transmitters that enabled the telemetric monitoring of activity and core body temperature (T-b) and bilaterally implanted with cranial guide t ubes that enabled the implantation of microdialysis probes into the striatu m. Striatal [GABA](ecf) was determined in unrestrained, non-hibernating gro und squirrels (T-b range 34.7-38.9 degrees C) and hibernating ground squirr els (T-b range 2.9-3.9 degrees C) using extrapolation to zero flow and very slow flow microdialysis techniques. The results show that [GABA](ecf) in n on-hibernating squirrels was 73 nM and this level was decreased by approxim ately 50% during hibernation thereby suggesting that an increase in [GABA]( ecf) does not play a major role in CNS depression during hibernation. The r eduction of [GABA](ecf) parallels a decrease in plasma and CSF [glucose] an d may be related to a decrease in GABA synthesis or reduced voltage depende nt release. This paper demonstrates that measurement of extracellular conce ntrations of neurotransmitters in animals with vastly different body temper atures is possible using microdialysis techniques of extrapolation to zero flow or very slow flow rates that enable 100% recovery. Such quantitative t echniques may prove valuable in the study of the neurochemistry of the cere bral mechanisms of hibernation and tolerance to cerebral ischemia exhibited by hibernating animals. (C) 1999 Published by Elsevier Science B.V. All ri ghts reserved.