The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit.
1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy. 2. Hypocapnic apnoea was used to study the fractional end-tidal CO2 (FET,CO2)-dependent tonic discharges of the expiratory motoneurones, the FET,CO2 threshold for rhythm generation and the FET,CO2 response curve of both inspiratory and expiratory burst activity. 3. Incremental doses of morphine (e.g. 1 mg kg-1 I.V.) produced slowing of the respiratory rhythm due to prolongation of the expiratory duration and an elevation of the FET,CO2 threshold for rhythm generation. Eventually apnoea supervened with associated tonic firing of the expiratory motoneurones. At the elevated levels of FET,CO2 bursts of inspiratory activity, with concomitant phasic inhibition of the tonic expiratory activity, could occur either spontaneously or following sensory stimulation. The peak integrated activities of these bursts were closely similar to the values obtained for corresponding levels of FET,CO2 before the administration of morphine. 4. Tonic expiratory activity responded to increased levels of FET,CO2, as it had during hypocapnic apnoea prior to morphine, by an increased discharge frequency of single units or recruitment of new units. 5. All of these effects of morphine were immediately reversed by naloxone (100 micrograms kg-1). 6. Naloxone (greater than 100 micrograms kg-1), without pre-treatment with morphine, led to an increase in respiratory frequency due to a shortening of the expiratory duration and a dose-dependent reduction in the FET,CO2 threshold for rhythm generation. There was little alteration either in the inspiratory response to FET,CO2 during rhythm or in the FET,CO2 response of the expiratory output whether expressed as tonic activity during hypocapnic apnoea or phasic activity following the onset of rhythm. 7. Thus opiates act upon the mechanisms of rhythm generation without depressing the FET,CO2 drive as expressed either as phasic or tonic activation of the motoneurones.
Howard
R S
RS
Sobell Department of Neurophysiology, Institute of Neurology, London.
Sears
T A
TA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D001239:Inhalation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D011817:Rabbits; D011999:Recruitment, Neurophysiological / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013909:Thorax / Q000294:innervation*; D013997:Time Factors
D009270:Naloxone; D009020:Morphine