GABA and homocarnosine in CSF: The relationship to brain GABA content

Abstract

GABA concentrations in cerebrospinal fluid (CSF) and brain of rats were determined before and after intraperitoneal injection of drugs that increase brain GABA levels. In untreated rats there is very little free GABA in the CSF (65 ± 12 pmol/ ml) but considerable amounts of conjugated GABA (2885 ± 100 pmol/ ml). Homocarnosine was identified as the major GABA conjugate (2110 ± 110 pmol/ ml). After administration of γ- vinyl GABA CSF concentrations of free GABA, total conjugated GABA and homocarnosine rise in a dose-dependent manner. There is an exponential correlation between whole brain GABA and free CSF GABA concentration. Brain GABA levels are linearly correlated with CSF concentrations of total conjugated GABA and homocarnosine. Ethanolamine-0-sulfate, at a dose not affecting brain GABA concentrations, markedly increases serum GABA but only minimally affects CSF GABA levels. This suggests that concentrations of GABA in the CSF are primarily related to brain GABA levels. Determination of CSF concentrations of free or conjugated GABA may be useful for the estimation of brain GABA levels in patients on therapy intended to alter brain GABA concentrations.