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

作者：Rick W Heckert, Daniel G Quock, Raymond M. Quock · 发表于：The FASEB Journal · 年份：2006 · DOI：10.1096/fasebj.20.4.a235-d · 研究领域：Anesthesia and Neurotoxicity Research、Eicosanoids and Hypertension Pharmacology、Anesthesia and Sedative Agents

Our laboratory has long studied the pharmacology of the anesthetic gas N 2 O, and we have implicated brain benzodiazepine receptors in N 2 O‐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 N 2 O 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% N 2 O in oxygen (O 2 ) for 1½ to 24 hr, removed to 100% O 2 (to reduce diffusion hypoxia) and placed in a room air environment to complete the washout of N 2 O. Thirty minutes following removal from N 2 O, mice were individually tested in the light/dark exploration test to determine behavioral responsiveness to 70% N 2 O in O 2 . Results show that it required a continuous exposure of 9 hr or longer of 70% N 2 O to induce tolerance to the anxiolytic‐like effects of a subsequent exposure to 70% N 2 O in the light/dark box paradigm. Preliminary results suggest that N 2 O‐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 N 2 O and possible cross‐tolerance to the effects of benzodiazepines. (Supported in part by NIH Grant DA‐10343.)