A non-invasive method for distinguishing central from peripheral nervous system effect 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 micrograms/kg sodium cyanide (peripheral stimulant) and comparing the changes in minute volume and mean inspiratory flow (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.
Murphy
D J
DJ
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA, USA.
Joran
M E
ME
Grando
J C
JC
D000818:Animals; D002344:Carotid Body / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects*; D003714:Denervation; D003864:Depression, Chemical; D008297:Male; D009020:Morphine / Q000494:pharmacology; D017933:Peripheral Nervous System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects*; D012966:Sodium Cyanide / Q000494:pharmacology
D009020:Morphine; D012966:Sodium Cyanide