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 hoo ded rats were tested in the conditioned defensive burying (CDB) test, a paradigm that exploits a propensity of rats to bury objects associat ed with aversive stimulation. A single, brief electrical shock was del ivered to rats upon contact with an electrified prod, before exposure to one of four mixtures of N2O and oxygen (O-2) (10-40% N2O) or room a ir (RA). Compared to RA-exposed animals, rats exposed to N2O exhibited a concentration-related reduction in duration and height of prod-dire cted ''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 buryi ng. Horizontal locomotion and rearing were not significantly affected at concentrations of N2O that attenuated prod-directed burying. Treatm ent with the benzodiazepine anxiolytic standard, chlordiazepoxide (2.5 -10.0 mg/kg) also resulted in dose-related attenuation of burying beha vior. These findings show that N2O can induce effects similar to those of known anxiolytics in this paradigm and suggest a benzodiazepine me chanism in its mediation.