Naloxone blocks suppression of cough by codeine in anesthetized rabbits

Opioid receptors which are involved in cough generation are abundantly expressed in the brainstem. Codeine is a potent μ-opioid receptor agonist. In the present study we examined the effects of naloxone, a μ-opioid receptor antagonist, on mechanically-induced tracheobronchial cough and on the cough suppressing effect of codeine in six pentobarbitone anesthetized spontaneously breathing rabbits. A single dose of naloxone (0.4 mg/kg) followed by a single dose of codeine (7 mg/kg) were administered intravenously. The number and amplitude of cough and sneeze reflexes were examined sequentially; before and after naloxone, and then after codeine. We found that neither did naloxone alone nor codeine given after prior naloxone pretreatment appreciably affect coughing or sneezing. Likewise, there were no significant differences in the diaphragm and abdominal muscles electromyographic moving averages, or the inspiratory and expiratory esophageal pressure amplitudes. However, we detected a tendency for the rise in expiratory motor drive during coughing and sneezing after injection of naloxone. The respiratory rate was significantly higher after naloxone in comparison with control (P < 0.001). No significant differences in arterial blood pressure were observed. We conclude that the failure of codeine to suppress the cough reflex on the background of naloxone pretreatment confirms the involvement of μ-opioid mechanism in the central antitussive effect of codeine.