Background: Previous research from our laboratory implicated opioid and benzodiazepine-
GABA mechanisms in other effects of N2O (antinociception and anxiolysis),
so a decision was made to study these as potential mechanisms of N2O-induced dysfunction
of spatial working memory.
Objective: to explore potential mechanisms of N2O in reducing spatial working memory in
Methods: we monitored spontaneous alternation behavior (SAB) in male NIH Swiss mice
exposed to N2O during a T-maze spontaneous alternation task (T-SAT).
Results: mice that were exposed to 70% N2O (in O2) exhibited severely and significantly
reduced spontaneous alternation behavior in the T-SAT. Mice in this environment alternated
their route only 33% of the time, in comparison to the control (room air) rate of alternation
at approximately 70%. Mice pretreated with the benzodiazepine antagonist, flumazenil
exhibited a dose-dependent restoration of spatial working memory under 70% N2O in the
T-SAT. Alternatively, pretreatment with neither the GABAA antagonist gabazine nor the
opioid antagonist naloxone had any appreciable effect on the N2O-reduced SAB.
Conclusion: this study verified that 70% N2O can reduce spatial working memory in mice,
which appears to involve benzodiazepine mechanisms in the brain.