title: Respiratory control of sympathetic nerve activity during naloxone-precipitated morphine withdrawal in rats.
abstract: In this study, we describe and compare the changes in phrenic nerve discharge and vasomotor sympathetic output produced by 1) acute administration of morphine in naive rats and 2) naloxone-precipitated withdrawal in morphine-dependent rats. Lumbar or splanchnic sympathetic nerve discharge and phrenic nerve discharge were recorded along with mean arterial pressure and end-expiratory CO2 in vagotomized, urethane-anesthetized, 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 baroreflex and the central respiratory drive of sympathetic nerve discharge. Subsequent administration of naloxone (1 mg/kg) reversed all cardiorespiratory effects of morphine and produced an overshoot, suggesting acute withdrawal. Morphine-dependent rats displayed a prolonged central inspiratory phase and a higher threshold for apnea. Naloxone-induced withdrawal was associated with an increase of mean arterial pressure and phrenic nerve discharge amplitude and a large reduction in the inspiratory phase. Withdrawal produced three distinct effects on sympathetic nerve discharge: 1) sensitization of the baroreflex, 2) large increase in the central respiratory drive and 3) selective increase in a respiratory-independent component of the splanchnic sympathetic outflow. It is concluded that the increase in central respiratory drive is a significant component of the sympathoactivation associated with naloxone-induced withdrawal.
authors: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville.
authors: S C
authors: SC
authors: Baraban
authors: R L
authors: RL
authors: Stornetta
authors: P G
authors: PG
authors: Guyenet
mesh_terms: D000818:Animals; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000502:physiology*; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D009270:Naloxone; D009020:Morphine