GABA in plasma and cerebrospinal fluid of different species. Effects of γ‐acetylenic GABA, γ‐vinyl GABA and sodium valproate

THE POSSIBLE role of GABA as an inhibitory neurotransmitter in mammalian brain led to the speculation that changes in GABA levels in the CNS may be associated with certain neurological disorders. Decreased levels of GABA and of glutam am ate I-carboxylase (EC 4.1.1.15), the enzyme responsible for the synthesis of GABA, have been determined in postmortem brains from patients with Huntington’s chorea (BIRD et al., 1973; PERRY et al., 1973). More recently, it has been found that the amount of GABA in the CSF of choreic patients is significantly lower as compared to control subjects (GLAESER et al., 1975; ENNA er al., 19770). The latter observation and the existence of a concentration gradient for GABA within the ventriculospinal fluid system (ENNA et al., 1977b) suggest that CSF GABA may reflect brain GABA concentrations. The measurement of GABA in CSF may therefore be useful both as a diagnostic test for certain disorders and in studying drug effects on brain GABA levels. However, accurate measurement of the low concentrations of GABA in CSF still poses analytical problems and only few relatively complicated methods are available which are sensitive and specific enough for this purpose. Whereas with the help of such techniques as liquid chromatography, gas chromatography-mass spectrometry and a radioreceptor assay GABA has been determined in picomole quantities in CSF of humans (GLAESER & HARE, 1975; GLAESER et a[., 1975; ENNA et al., 1977a,h; HUIZINGA et al., 1977; BOHLEN et al., 1978; COLBY & MCCAMAN, 1978; WOOD et al., 197%) and rats (HUOT ef al., 1978), reports on CSF GABA concentrations in dogs (LOGOTHETIS, 1958) and cats (SNODGRASS er al., 1969) showed much higher values and probably reflect inadequacies of the methods used. More recently, GABA has also been detected in low concentrations in blood and plasma of different species including man (FERKANY et al., 1978; HUOT et ul., 1978). In the present study, the GABA concentrations in CSF and plasma of dog, cat and rat were determined and compared with those of man using the radioreceptor assay of ENNA et al. (19776). Furthermore, preliminary experiments on the effect of agents known to increase brain GABA on the concentration of this amino acid in CSF and plasma are reported