Glutamate decarboxylase activity in the substantia nigra and the hippocampus of rats microinjected with inhibitors of the enzyme.

Three inhibitors of glutamate decarboxylase (GAD), acting through different mechanisms, as well as pyridoxal phosphate (PLP), were microinjected unilaterally by stereotaxic procedures into the substantia nigra reticulata or the CA1 area of the hippocampus of the rat. The inhibitors used were thiosemicarbazide (TSC), gamma-glutamyl hydrazide and the PLP-glutamyl-hydrazone (PLPGH) formed by the combination of the latter with PLP. No behavioral alterations were observed after the administration of any of the drugs used, in any of the two brain regions studied. When measured in the absence of exogenous PLP, GAD activity in the substantia nigra injected with TSC was diminished by about 35%, and no changes were observed with the other drugs. In the CA1 hippocampal area both TSC and PLPGH inhibited GAD by more than 50%, and this inhibition was not reversed by PLP added in vitro. The results are discussed in terms of the possible explanation for the differences between the drugs used and for the lack of effects of GAD inhibition on the behavior of the animals.