Affiliation:
1. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Abstract
Hyperbaric oxygen (HBO2) inhibits GABAergic neurotransmission in the brain, which can lead to the development of a seizure disorders known as “oxygen epilepsy”. Deficiency in GABAergic transmission in HBO2, resulting from a decrease in the level of synaptic GABA, can be compensated by inhibition of neuronal and glial GABA transporters (GAT). The present study compared the anticonvulsant efficacy of two types of GABA transporters with tiagabine, a GAT-1 inhibitor, and SNAP 5114, a GAT-3 inhibitor. Anticonvulsant effects were assessed after administration of drugs into the lateral cerebral ventricle of rats 30 min before the start of hyperbaric oxygen exposure at 5 ATA. In separate experiments, the concentration of GABA in the striatum of rats was measured when breathing oxygen at a pressure of 5 ATA after GAT inhibition with tiagabine or SNAP 5114. New results obtained in the study were: (1) inhibition of GAT-1 or GAT-3 prevented the development of “oxygen epilepsy” in rats; (2) among the two inhibitors used, TGB was found to be more effective in preventing oxygen convulsions compared to SNAP 5114; (3) the combined use of TGB + SNAP 5114 caused an additive anticonvulsant effect; (4) oxygen convulsions appeared when GABA in the brain decreased by 30–40% of the initial level; (5) GAT-1 inhibition with tiagabine increased extracellular GABA 2.9-fold and 1.7-fold with SNAP 5114. GAT-1 and GAT-3 inhibition increased GABA to a level sufficient to restore impaired inhibitory neurotransmission in HBO2, and prevented the development of hyperbaric oxygen convulsions.
Publisher
The Russian Academy of Sciences
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