Central nervous system toxicity of hyperbaric oxygen-effects of light, norepinephrine depletion and beta-adrenergic blockade ☆

Abstract Male Swiss-Webster mice exposed to hyperbaric oxygen (OHP. 4 atmospheres, absolute) in relative darkness (4 ft-candle) developed clonic and tonic seizures and 50% of the animals convulsed within 15–20 min. The incidence of seizures during a 30 min period averaged 82'%. In the light (130 ftcandle), OHP-induced seizures were delayed: 50% of mice convulsed in 24.2 min, and the incidence of seizures was reduced to 54%. Blinded mice exposed to OHP in the light had similar onset and incidence of seizures as intact mice exposed to OHP in the dark. Selective depletion of brain norepinephrine by pretreatment with FLA-63. a dopamine-β-hydroxylase inhibitor, or with 6-OH dopa combined with carbidopa, significantly delayed the onset and reduced the incidence of OHP-induced seizures. β-Adrenergic blockade using dl - and l -propranolol also protected mice from OHP-induced seizures. d -Propranolol had no effect. These results suggest that the availability and release of norepinephrine, and the action of norepinephrine on central β-adrenergic receptors play a role in the genesis of central nervous system toxicity of OHP.