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 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.
Baraban
S C
SC
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville.
Stornetta
R L
RL
Guyenet
P G
PG
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*
D009270:Naloxone; D009020:Morphine