Nitrous oxide induces an anxiolytic-like effect in the conditioned defensive burying paradigm, which can be reversed with a benzodiazepine receptor blocker.
To investigate the anxiolytic effects of nitrous oxide (N2O), male hooded rats were tested in the conditioned defensive burying (CDB) test, a paradigm that exploits a propensity of rats to bury objects associated with aversive stimulation. A single, brief electrical shock was delivered to rats upon contact with an electrified prod, before exposure to one of four mixtures of N2O and oxygen (O2) (10-40% N2O) or room air (RA). Compared to RA-exposed animals, rats exposed to N2O exhibited a concentration-related reduction in duration and height of prod-directed "defensive" burying with floor bedding material; these measures reached statistical significance at 30% N2O. Pretreatment with 20 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, effectively antagonized a 30% N2O-induced decrease in burying. Horizontal locomotion and rearing were not significantly affected at concentrations of N2O that attenuated prod-directed burying. Treatment with the benzodiazepine anxiolytic standard, chlordiazepoxide (2.5-10.0 mg/kg) also resulted in dose-related attenuation of burying behavior. These findings show that N2O can induce effects similar to those of known anxiolytics in this paradigm and suggest a benzodiazepine mechanism in its mediation.
Department of Psychology (SC-454), Marquette University, Milwaukee, WI 53233.
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats
D014151:Anti-Anxiety Agents; D058787:GABA-A Receptor Antagonists; D005442:Flumazenil; D002707:Chlordiazepoxide; D009609:Nitrous Oxide