The relationship between GABA concentrations in brain and cerebrospinal fluid

Abstract

GABA concentrations in cerebrospinal fluid (CSF) and brain of rats and cats were determined before and after i.p. of 3 drugs [.gamma.-vinyl GABA, .gamma.-acetylenic GABA, ethanolamine-O-sulfate] that increase brain GABA levels. GABA exists in the CSF in 2 forms: free and conjugated GABA. In the CSF of untreated animals, there is very little free GABA (65 .+-. 12 pmol/ml) but considerable amounts of conjugated GABA (2885 .+-. 100 pmol/ml). After i.p. administration of .gamma.-vinyl GABA to rats, CSF concentrations of both free and conjugated GABA rise in a dose-dependent manner. There is an exponential correlation (r = 0.92, P < 0.001) between rat whole brain GABA concentrations and free GABA in the CSF. Concentrations of brain GABA and conjugated CSF GABA are linearly correlated (r = 0.84, P < 0.001). .gamma.-Acetylenic GABA has qualitatively similar effects to .gamma.-vinyl GABA. Treatment with ethanolamine-O-sulfate i.p. at a dose not affecting brain GABA concentrations markedly increases serum GABA, leaves conjugated CSF GABA unchanged and significantly elevates free GABA in the CSF. Total CSF GABA concentrations are related primarily to brain GABA levels and are minimally affected by changes in the peripheral GABA concentrations. Determination of the levels of free and conjugated GABA in the CSF may be useful for the estimation of brain GABA concentration in [human] patients on therapy intended to alter brain GABA levels.