Abstract <p>The use of hyperbaric oxygen (HBO₂)in medicine and underwater diving is associated with the risk of itstoxic (convulsant) effects on the CNS, whose pathophysiologicalmechanisms remain insufficiently studied. A common hypothesis regardingthe mechanism of HBO₂-induced seizures suggeststhat extreme hyperoxia suppresses GABAergic function, followed byincreased CNS excitation leading, in turn, to seizures. While thedeficit in GABAergic function under HBO₂ isattributed to reduced neurotransmitter synthesis, the involvementof other components of inhibitory neurotransmission, specificallyGABA receptors, remains unclear. The aim of this study was to investigatethe role of GABA receptors in the development of HBO₂-inducedseizures. In this work, motor seizures under HBO₂ were assessedin rats administered intracerebroventricularly with GABA receptoragonists, muscimol or baclofen, prior to hyperoxic exposure. Theaffinity of GABA receptors for these drugs was evaluated also againsta background of elevated brain GABA levels, induced by intracerebroventricularadministration of nipecotic acid. The key findings of this studyare the following. (a) Activation of GABA-A receptors with muscimoldelayed the onset of seizures under HBO₂;(b) the GABA-B receptor agonist baclofen attenuated the developmentof HBO₂-induced seizures, although its anticonvulsanteffect was significantly weaker than that of muscimol; (c) anticonvulsantefficacy of muscimol and baclofen persisted under conditions ofelevated extracellular GABA levels, caused by the inhibition ofGABA transporters with nipecotic acid. The affinity of GABA-A andGABA-B receptors for the inhibitory neurotransmitter remained unchangedunder hyperbaric hyperoxia.</p>