RESPIRATORY CONTROL OF SYMPATHETIC-NERVE ACTIVITY DURING NALOXONE-PRECIPITATED MORPHINE-WITHDRAWAL IN RATS

In this study, we describe and compare the changes in phrenic nerve di scharge and vasomotor sympathetic output produced by 1) acute administ ration of morphine in naive rats and 2) naloxone-precipitated withdraw al in morphine-dependent rats. Lumbar or splanchnic sympathetic nerve discharge and phrenic nerve discharge were recorded along with mean ar terial pressure and end-expiratory CO2 in vagotomized, urethane-anesth etized, paralyzed and artificially ventilated rats. Acute injection of morphine (1 and 5 mg/kg, i.v.) reduced resting mean arterial pressure , resting phrenic nerve discharge amplitude, the sympathetic barorefle x and the central respiratory drive of sympathetic nerve discharge. Su bsequent administration of naloxone (1 mg/kg) reversed all cardiorespi ratory effects of morphine and produced an overshoot, suggesting acute withdrawal. Morphine-dependent rats displayed a prolonged central ins piratory phase and a higher threshold for apnea. Naloxone-induced with drawal was associated with an increase of mean arterial pressure and p hrenic nerve discharge amplitude and a large reduction in the inspirat ory phase. Withdrawal produced three distinct effects on sympathetic n erve discharge: 1) sensitization of the baroreflex, 2) large increase in the central respiratory drive and 3) selective increase in a respir atory-independent component of the splanchnic sympathetic outflow. It is concluded that the increase in central respiratory drive is a signi ficant component of the sympathoactivation associated with naloxone-in duced withdrawal.