Abstract

Experimental mice, but not control mice, were exposed to airflow-hypoxia for 30 minutes daily for at least 6 days. Twenty-four hours after the last exposure session, all mice were tested with or without a test exposure to airflow-hypoxia or airflow alone. In the control mice, airflow-hypoxia prolonged the duration of hexobarbital narcosis, decreased the rate of in vivo hexobarbital metabolism and lowered rectal temperature. In the experimental mice, airflow-hypoxia did not produce any of those changes. In addition, in the presence of airflow-hypoxia, the experimental mice did not differ from the control mice with respect to duration of narcosis due to unmetabolizable sodium barbital or the body levels of hexobarbital remaining at the time of recovery from hexobarbital narcosis. Airflow without hypoxia did not alter action of hexobarbital in the control mice. But, in the experimental mice, airflow without hypoxia in and by itself caused a 20-35% reduction in the duration of hexobarbital narcosis, 1-2°C elevation in rectal temperature and an enhancement of in vivo hexobarbital metabolism. The magnitudes of reduction in hexobarbital narcosis and of elevation in rectal temperature were proportional to the number of prior daily sessions in which airflow was paired with hypoxia. The airflow lost its effectiveness in the experimental mice after those mice were further exposed to six sessions of airflow without pairing it with hypoxia. The effects of airflow when applied alone during testing are interpreted as being due to stimulus control which usually takes place after conditioning. In this case a neutral stimulus after prior repeated pairing with hypoxia in itself came to exert well-defined physiological effects. This interpretation was further strengthened by the observation that the effects of airflow could be extinguished. In vitro experiments showed that the reduction in hexobarbital narcosis was correlated with increased activity of the hepatic microsomal enzyme system which metabolizes hexobarbital and demethylates p-nitroanisole. It was not correlated with changes in the activity of microsomal cytochrome P-450 or microsomal cytochrome c reductase.