Fig. 4. (A ) The influence of saline (0 mg/kg morphine) and three morphine doses on the slope of the hypercapnic ventilatory response. Values are mean ± SD. Analysis of variance: * P < 0.05 versus all other treatment levels. (B ) Mean values ± SD of the slope of ventilation versus carbon dioxide in μ-opioid receptor (OR)−/−and μOR+/+mice after various treatments. S = saline; M = 100 mg/kg morphine; N = 100 μg/kg naloxone; NM = combined administration of 100 mg/kg morphine and 100 μg/kg naloxone. Morphine reduced the slope of the hypercapnic ventilatory response (HCVR) in wild-type mice only, whereas naloxone increased the slope in mutant and wild-type animals. Note the absence of effect of morphine after naloxone pretreatment in wild-type animals (pharmacologic knockout). * P < 0.0001 (paired comparison); ** P = 0.02 (unpaired comparison).