Development of tolerance to nitrous oxide (N2O)‐induced anxiolysis and cross‐tolerance to chlordiazepoxide (CP) in mice

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A235-A236
• Main Authors: Heckert, Rick W, Quock, Daniel G, Quock, Raymond M
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A235-d

Our laboratory has long studied the pharmacology of the anesthetic gas N2O, and we have implicated brain benzodiazepine receptors in N2O‐induced anxiolytic effects (Li and Quock, Pharmacol. Biochem. Behav. 68:789‐796, 2001). This study was conducted to determine the extent to which tolerance develops to the anxiolytic effect of N2O and whether there is cross‐tolerance to the anxiolytic effects of the benzodiazepine CP. Male NIH Swiss mice, 18–30 g, were exposed to 70% N2O in oxygen (O2) for 1½ to 24 hr, removed to 100% O2 (to reduce diffusion hypoxia) and placed in a room air environment to complete the washout of N2O. Thirty minutes following removal from N2O, mice were individually tested in the light/dark exploration test to determine behavioral responsiveness to 70% N2O in O2. Results show that it required a continuous exposure of 9 hr or longer of 70% N2O to induce tolerance to the anxiolytic‐like effects of a subsequent exposure to 70% N2O in the light/dark box paradigm. Preliminary results suggest that N2O‐tolerant mice also exhibited reduced responsiveness to the anxiolytic‐like effects of some doses of CP when compared to control mice that were exposed for an equal period of time to compressed air. These results provide evidence for development of tolerance of mice to the anxiolytic effects of N2O and possible cross‐tolerance to the effects of benzodiazepines. (Supported in part by NIH Grant DA‐10343.)