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Current Psychopharmacology


ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

Research Article

Nitrous Oxide-induced Impairment of Spatial Working Memory Requires Activation of GABAergic Pathways

Author(s): Dimitris E. Emmanouil*, Evan D. Klein, Katherine Chen, Abigail L. Brewer, Yangmiao Zhang and Raymond M. Quock

Volume 9 , Issue 1 , 2020

Page: [68 - 78] Pages: 11

DOI: 10.2174/2211556009666200217121518

Price: $65


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 mice.

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.

Keywords: Amnesia, flumazenil, gabazine, mouse, naloxone, nitrous oxide, spatial memory.

Graphical Abstract
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