Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Abstract

The concentrations of GABA, glutamate, serine, glutamine, threonine, glycine and taurine in the substantia nigra and in the corpus striatum of the rat were determined electrochemically following condensation with o-phthalaldehyde-beta-mercaptoethanol and reverse-phase, high performance liquid chromatography. After a frontal hemisection at the level of the caudal hypothalamus, the GABA concentration in the substantia nigra on the operated side decreased to about 20 per cent of the normal value in 4 days, in all probability caused by degeneration of the nerve terminals of the striato-nigral GABA neurons. The concentrations of taurine in the substantia nigra and of GABA in the corpus striatum were initially lowered and later elevated following this lesion. The concentration of glutamate in the substantia nigra was lower on the sectioned side and higher on the intact side at 14 days as compared to 4 hours after a hemisection. Following an acute hemisection, the GABA transaminase inhibitor gamma-acetylenic GABA increased the concentration of GABA by 36% and 79% in the substantia nigra on the sectioned and intact side, respectively. The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side. The results indicate that the synthesis, but not the utilization of GABA in the substantia nigra is dependent on the normal nerve impulse flow. The concentration of glutamine was changed in directions contrary to that of GABA following a chronic hemisection or treatment with gamma-acetylenic GABA, in agreement with the suggestion that glutamine is a precursor of the GABA transmitter pool.