Respiration of hyperbaric oxygen (HBO2) suppresses the synthesis of γ-aminobutyric acid (GABA) in the brain, leading to weakening of inhibitory GABAergic neurotransmission and the development of convulsive syndrome of the epileptic seizure type. We report here our testing of the hypothesis that inhibition of GABA transporters might compensate for insuffi ciency of inhibitory transmitter synthesis, strengthen GABAergic transmission, and weaken or prevent the development of oxygen-induced convulsions. The development of convulsions was studied in conscious rats in a barochamber containing oxygen at a pressure of 5 atm (absolute atmospheres) after prior intracerebroventricular administration of drugs inhibiting selective neuronal (NO-711) or nonselective neuronal/glial GABA transporters (nipecotic acid). Studies in a separate group of rats measured GABA in the striatum by microdialysis with liquid chromatography. These experiments showed that inhibition of neuronal and glial GABA transporters increases the level of GABA in the brain and weakens the development of oxygen-induced convulsions. A more effective anticonvulsant effect was seen after intracerebroventricular administration of the nonselective inhibitor of GABA transporters. These data provide evidence that blockade of the functions of neuronal and glial GABA transporters increases the GABA level in the brain and weakens the development of convulsive syndrome in HBO2. The anticonvulsant effects of the inhibitors used here appear to result from strengthening of GABA-mediated synaptic and extrasynaptic neurotransmission by hyperbaric hyperoxia. Inhibition of GABA transporters may constitute a potential direction for the development of effective methods of preventing oxygen-induced convulsions.
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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 4, pp. 510–519, April, 2019.
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Moskvin, A.N., Platonova, T.P., Zhilyaev, S.Y. et al. Blockade Of γ-Aminobutyric Acid Transporters In Brain Synapses Protects Against Hyperbaric Oxygen-Induced Convulsions. Neurosci Behav Physi 50, 505–510 (2020). https://doi.org/10.1007/s11055-020-00930-1
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DOI: https://doi.org/10.1007/s11055-020-00930-1