The Role of GABA Receptors in Seizure Development When Breathing Hyperbaric Oxygen

The use of hyperbaric oxygen (HBO2) in medicine and underwater diving is associated with the risk of its toxic (convulsant) effects on the CNS, whose pathophysiological mechanisms remain insufficiently studied. A common hypothesis regarding the mechanism of HBO2-induced seizures suggests that extreme hyperoxia suppresses GABAergic function, followed by increased CNS excitation leading, in turn, to seizures. While the deficit in GABAergic function under HBO2 is attributed to reduced neurotransmitter synthesis, the involvement of other components of inhibitory neurotransmission, specifically GABA receptors, remains unclear. The aim of this study was to investigate the role of GABA receptors in the development of HBO2-induced seizures. In this work, motor seizures under HBO2 were assessed in rats administered intracerebroventricularly with GABA receptor agonists, muscimol or baclofen, prior to hyperoxic exposure. The affinity of GABA receptors for these drugs was evaluated also against a background of elevated brain GABA levels, induced by intracerebroventricular administration of nipecotic acid. The key findings of this study are the following. (a) Activation of GABA-A receptors with muscimol delayed the onset of seizures under HBO2; (b) the GABA-B receptor agonist baclofen attenuated the development of HBO2-induced seizures, although its anticonvulsant effect was significantly weaker than that of muscimol; (c) anticonvulsant efficacy of muscimol and baclofen persisted under conditions of elevated extracellular GABA levels, caused by the inhibition of GABA transporters with nipecotic acid. The affinity of GABA-A and GABA-B receptors for the inhibitory neurotransmitter remained unchanged under hyperbaric hyperoxia.