3-Nitropropionic acid exacerbates [3H]GABA release evoked by glucose deprivation in rat striatal slices.

3-Nitropropionic acid (3-NPA) is a metabolic poison that produces lesions of striatal intrinsic neurones such as gamma-aminobutyric acid (GABA) neurones. This study was carried out to determine whether 3-NPA would impair the ability of striatal GABAergic neurones to withstand hypoglycaemic stress. 3-NPA (500 microM) did not affect [3H]GABA release from striatal slices under normal (11 mM) glucose concentrations. When the glucose concentration was lowered to 0.3 mM, however, 3-NPA greatly potentiated the leakage of [3H]GABA from the slices. Blockage of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors with 1 microM 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) or 10 microM 2,3-dihydroxy-6-nitro-7-sulpha-moylbenzo[F]quinoxaline (NBQX), respectively, or a combination of both, had no effect. However, blockade of voltage-dependent sodium channels with tetrodotoxin totally antagonized the [3H]GABA overflow induced by the combination of 3-NPA and hypoglycaemis. Riluzole (10 to 100 microM), a neuroprotective agent that stabilizes the inactivated state of the voltage-dependent sodium channel, also dose-dependently antagonized the increase in [3H]GABA release induced by the combination of the two stresses.