A NONINVASIVE METHOD FOR DISTINGUISHING CENTRAL FROM PERIPHERAL NERVOUS-SYSTEM EFFECTS OF RESPIRATORY DEPRESSANT DRUGS IN CONSCIOUS RATS

1. A simple, non-invasive method for distinguishing the central from peripheral effects of respiratory depressant drugs was developed in conscious rats. 2. The procedure involves exposing rats for 5 min to an air mixture containing 8% CO2 (central stimulant) followed by an i.v. bolus injection of 300 mu g/kg sodium cyanide (peripheral stimulant) and comparing the changes in minute volume and mean inspiratory Bow (respiratory drive) before and after drug treatment. 3. The central depressant drugs morphine, xylazine, L-2-phenylisopropyladenosine (L-PIA) and gamma-hydroxybutyric acid (GHBA) inhibited the CO2-induced increase in minute volume and enhanced the sodium cyanide-induced increase in mean inspiratory flow. 4. Peripheral depression produced by carotid body denervation had no effect on the CO2-induced increase in minute volume and inhibited the sodium cyanide-induced increase in mean inspiratory flow.