Involvement of vagal opioid receptors in respiratory effects of morphine in anaesthetized rats

Respiratory effects of morphine injection to the femoral vein were investigated in urethane and chloralose anaesthetized and spontaneously breathing rats, prior to and after midcervical vagotomy. Bolus injection of morphine HCl at a dose of 2 mg/kg of body weight induced depression of ventilation in all rats, due to the significant decrease in tidal volume and to the decline in respiratory rate both pre- and post-vagotomy. Expiratory apnoea of mean duration of 10.0 +/- 3.4 s was present in the vagally intact rats only. Bilateral midcervical section of the vagus nerve precluded the occurrence of apnoea. Prolongation of the expiratory time (T-E morphine / T-E control) which amounted to 10.7 +/- 2.2-fold in the intact state, was apparently reduced to 1.5 +/- 0.3-fold after division of the vagi. Morphine significantly decreased mean arterial pressure (MAP) at 30 s after the challenge, the effect persisted for not less than 1 minute and was absent in vagotomized rats. The respiratory changes evoked by morphine reverted to the control level after intravenous injection of naloxone at a dose of 1 mg/kg. Results of this study indicate that opioid receptors on vagal afferents are responsible for the occurrence of apnoea and hypotension evoked by morphine.