Abstract <p>The use of hyperbaric oxygen (HBO₂)in clinical practice and during commercial or military diving is associatedwith the risk of its toxic effects on the central nervous system,the pathophysiological mechanisms of which remain poorly understood.It is hypothesized that HBO₂ exerts an activatingeffect on the glutamatergic system, leading to increased CNS excitabilityand the subsequent development of hyperbaric oxygen seizures, phenotypicallysimilar to epileptic seizures. The objective of this study was to investigatethe role of glutamate NMDA receptors in the development of seizuresyndrome induced by extreme hyperoxia. We evaluated seizure developmentin rats administered drugs that activate (methionine sulfoximine,MSO) or block (memantine or MK-801) glutamate NMDA receptors priorto HBO₂ exposure. The anticonvulsant efficacyof the drugs was assessed by the latency of hyperbaric oxygen seizures.It was found that increasing synaptic glutamate levels by inhibitingglutamine synthetase with MSO accelerated the onset of generalized motorseizures, whereas blocking NMDA receptors with MK-801 or memantinedid not prevent the development of seizure syndrome. Morphological examinationof brain tissue revealed a decrease in the count of viable pyramidalneurons and the presence of hyperchromic neurons in the hippocampalCA3 field of animals exposed to HBO₂. Memantine administrationto animals prior to HBO₂ exposure showedno significant difference in the count of viable pyramidal neuronscompared to untreated animals, suggesting the absence of a pronounced neuroprotectiveeffect of the drug under these conditions. The results indicatethe involvement of the glutamatergic system in the pathogenesisof hyperbaric oxygen-induced seizures, although glutamate NMDA receptorsdo not appear to play a critical role in initiating seizure activity.</p>