title: Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons.
abstract: Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 microg/kg) of the mu-opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2-4 microg/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.
authors.affiliation: Dept. of Physiology, Medical Sciences Center, Univ. of Wisconsin, 1300 Univ. Ave., Madison, WI 53706, USA. pmlalley@facstaff.wisc.edu
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lalley
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005283:Fentanyl