Use of GABA-T Inhibitors

Expenments in our laboratory have shown that about 50% of the GABA-T activity must be inhibited to give an adequate increase in GABA level in the brain (Omholt-Jensen, 1984). There are three basic conditions that must be fulfilled if GABA-T inhibitors are used to study GABA turnover. 

The physiological effects that are unwanted in turnover studies may be modified by using lower doses of GABA-T inhibitors or by applying the inhibitors intracerebrally to avoid systemic effects 

GABA after systemic injection is relatively smaller after 1 h than after 3 h (Walters et al., 1978). The method has been used to show a reduced turnover of GABA in striatum and substantia nigra after apomorphme administration (Hokfelt et al., 1976). 

L-Cycloserine is an inhibitor of several aminotransferases, including GABA-T. It interacts with pyridoxal phosphate and therefore inhibits GAD, although to a lesser extent than GABA-T (Dann and Carter, 1964). 

It is well recognized that there is a rapid postmortal increase of GABA m the brain (Minard and Mushahwar, 1966). The increase is caused by GABA synthesis proceeding initially at the same rate postmortem as in vivo, and an almost complete inhibition of GABA catabolism by anoxia. The latter occurs because GABA transamination requires 2-oxoglutarate for transamination and oxidized NAD for the oxidation of succinic semialdehyde. 

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