Premedication as an important component of pre-anesthetic drugs can be either very useful or dangerous and may disrupt the outcome of a surgery. For example, premedication dexamethasone may change normal body responses to stressors such as acute hypoxia through various mechanisms, such as inhibiting the pituitary-hypothalamic axis. Using nonselective nitric oxide synthase inhibitors (10mg/kg L-Name) and a selective neuronal blocker (40mg/kg NOS 7-NI), this study did not prevent the negative effects of dexamethasone as a premedication. Concomitant injection of dexamethasone 0.2 mg/kg as a pretreatment, a NO precursor blocker (L-arginine 60mg/kg) and an NMDA receptor blocker (0.5mg/kg Ketamine) 30 minutes before acute hypoxia also could not be a stimulus for adult mice normal responses to hypoxia. The results of this study showed that injection of premedication dexamethasone at a dose of 0.2mg/kg or higher three days before surgery decreased the response to acute hypoxia and disrupted Tail Test 60 minutes after hypoxia in the adult mouse completely and its effect remained for several hours.