Nitrous oxide induces an anxiolytic-like effect in the conditioned defensive burying paradigm, which can be reversed with a benzodiazepine receptor blocker

Abstract

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.

GABA enhancement of maternal defense in mice: Possible neural correlates

“…At the very least, the lack of overt change in a number of maternal behaviors examined suggests CDP did not overtly affect motor behaviors. In addition, past literature support that low doses of CDP (0.5-5 mg/ kg) have no effect on locomotion (Kennett et al, 1997;Leveleki et al, 2006;Nicholls et al, 1992) or increased mobility (Choleris et al, 2001;Czech and Quock, 1993;Varty et al, 2003) in rodents. Although rodents in the above studies were not in the postpartum period, the results do support the idea that 1 mg/kg of CDP was not producing sedative side effects in this study.…”

An additive factor analysis of the effect of sub-anaesthetic doses of nitrous oxide on information processing: evidence for an impairment of the motor adjustment stage

“…These effects appear to be related to opioid and/or benzodiazepine-like actions (Hynes and Berkowitz 1979;Gillmann et al 1986;Quock et al 1992;Czech and Quock 1993;Emmanouil et al 1994;Czech 1995;Courtire and Hardouin 1997). The subjective, behavioral and cognitive effects of subanaesthetic doses of N 2 O have been studied in humans (Garfield et al 1975;Fowler et al 1983Fowler et al , 1985Fowler et al , 1988Fowler et al , 1989Zacny et al 1994;Cheam et al 1995;Fried et al 1995;Galinkin et al 1997) and may be investigated by using the reaction time (RT) paradigm.…”

The age of anxiety: role of animal models of anxiolytic action in drug discovery

“…Benzodiazepines, phenobarbitol, acute vigabatrin, zolpidem, buspirone, acute fluoxetine, ondansetron, propanolol (Crawley, 1981;Lucki et al, 1989;Stefań ski et al, 1992;Sherif and Oreland, 1995;de Angelis, 1996;Schmitt and Hiemke, 1998;Prut and Belzung, 2003) Defensive (Treit et al, 1981;Craft et al, 1988;Njung'e and Handley, 1991;Czech and Quock, 1993;Picazo and Fernández-Guasti, 1995;De Boer and Koolhaas, 2003;Joel, 2006) Ultrasonic vocalizations Mouse pups are separated from their mothers and the frequency of ultrasonic distress calls is recorded A reduction in the number of USVs emitted from separated pups is regarded as an anxiolytic effect.…”