An anxiolytic-like effect of hyperbaric oxygen in the mouse light/dark exploration test

Abstract

Aims: We studied whether hyperbaric oxygen (HBO(2)) treatment, which is known to increase production of nitric oxide (NO) in the brain, might also produce an NO-dependent anxiolytic-like behavioral response.

Main methods: Male NIH Swiss mice (20-25g) were subjected to a 60-min HBO(2) treatment at different absolute atmospheres, and anxiety was assessed using the light/dark exploration test at different time intervals following the cessation of HBO(2) treatment. To ascertain the underlying mechanism of action, other groups of mice were pretreated with the NO synthase inhibitor N(G)-monomethyl-l-arginine acetate, the NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO), the soluble guanylyl cyclase-inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the benzodiazepine antagonist flumazenil to determine their influence on the HBO(2)-induced anxiolytic-like effect.

Key findings: A 60-min HBO(2) treatment at 3.0 absolute atmospheres increased the time spent by mice in the light compartment that lasted up to 90 min following the end of HBO(2) treatment. This anxiolytic effect of HBO(2) was significantly reduced by pretreatment with L-NMMA, carboxy-PTIO, ODQ and flumazenil.

Significance: Based on these findings, we conclude that a 60-min HBO(2) treatment is capable of inducing an anxiolytic effect that possibly involves NO, cyclic GMP and the benzodiazepine binding site.