Glutamate decarboxylase activity in the substantia nigra and the hippocampus of rats microinjected with inhibitors of the enzyme
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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), γ-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.
Key WordsGlutamate decarboxylase substantia nigra hippocampus pyridoxal phosphate stereotaxic injections
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- 2.Tapia, R. 1975. Biochemical pharmacology of GABA in CNS. Pages 1–58,in Iversen, L. L., Iversen, S. D., and Snyder S. H. (eds.) Handbook of Psychopharmacology, Vol. 4, Plenum Press, New York.Google Scholar
- 3.Meldrum, B. S. 1975. Epilepsy and gamma-aminobutyric acid-mediated inhibition. Intern. Rev. Neurobiol. 17:1–36.Google Scholar
- 4.Tower, D. B. 1976. GABA and seizures: clinical correlates in man. Pages 461–478,in Roberts, E., Chase, T.N., and Tower, D. B. (eds.) GABA in Neuvous System Function. Raven Press, New York.Google Scholar
- 5.Lloyd, K. G. 1987. Psychopharmacology of GABAergic drugs. Pages 183–195,in Meltzer, H. Y. (ed.) Psychopharmacology: The Third Generation of Progress. Raven Press, New York.Google Scholar
- 10.Tapia, R., Pasantes, H., Ortega, B. G., and Massieu, G. H. 1966. Effects in vivo and in vitro ofl-glutamic acid-γ-hydrazide on metabolism of some free amino acids in brain and liver. Biochem. Pharmacol. 15:1831–1845.Google Scholar
- 14.Sah, J. 1954. Nicotinyl and isonicotinyl hydrazones of pyridoxal. J. Amer. Chem. Soc. 76:300.Google Scholar
- 15.König, J. F. R., and Klippel, R. A. 1963. The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Williams and Wilkins, Baltimore.Google Scholar
- 16.Paxinos, G., and Watson, C. 1986. The Rat Brain in Stereotaxic Coordinates. Academic Press, Sidney.Google Scholar
- 22.Turski, L., Cavalheiro, E. A., Schwarz, M., Turski, W. A., de Moraes Mello, L. E. M., Bortolotto, Z. A., Klockgether, T., and Sontag, K.-H. 1986. Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or γ-vinyl-GABA into the substantia nigra. Brain Res. 370:294–309.PubMedGoogle Scholar