The effects of opiates on respiration, nociception and core temperature in rats

Animals exposed to 5, 7.5, 10, 20, or 40 mg/kg of morphine s.c. or to 2, 6.5 or 15 mg/kg of levorphanol s.c. exhibited dose-dependent hypercapnia, hypoxemia and acidosis, as well as dose-dependent changes in analgesic threshold. Levorphanol produced more severe and longer lasting changes in respiratory parameters and analgesic response times than did equimolar doses of morphine. Dextrorphan tartrate administration (25.5 mg/kg) s.c. did not produce changes in respiratory parameters or analgesic response. Concurrent administration of 5 mg/kg naloxone s.c. with 15 mg/kg levorphanol s.c. prevented the respiratory changes and analgesic response observed when levorphanol was administered alone. These results indicate that the respiratory depressant and analgesic effects of opiates are stereospecific and naloxone reversible. The stereo-specificity and naloxone reversal of these effects confirms that these responses are mediated by a specific opiate receptor. The fact that analgesia and respiratory changes correlated very closely in a temporal fashion does not necessarily support the theory that these two effects are mediated by separate receptors. No temperature changes were produced by these opiates. These results suggest that if there is a receptor which mediates temperature changes, it is separate from the receptor(s) which mediate analgesia and respiratory depression.