Dopamine1 receptor agonists reverse opioid respiratory network depression, increase CO2 reactivity.
In adult pentobarbital-anesthetized and unanesthetized decerebrate cats, the D(1)R agonists (6-chloro-APB, SKF-38393, dihydrexidine) given intravenously restored phrenic nerve and vagus nerve respiratory discharges and firing of bulbar post-inspiratory neurons after the discharges were abolished by the micro-opioid receptor agonist fentanyl given intravenously. Reversal of opioid-mediated discharge depression was prevented by the D(1)R antagonist SCH23390. Iontophoresis of the micro-opioid receptor agonist DAMGO depressed firing of medullary bulbospinal inspiratory neurons. Co-iontophoresis of SKF-38393 did not restore firing and had no effect on bulbospinal inspiratory neuron discharges when applied alone. The D(1)R agonists given intravenously prolonged and intensified phrenic nerve and bulbospinal inspiratory neuron discharges. They also increased reactivity to CO(2) by lowering the phrenic nerve apnea threshold and shifting the phrenic nerve-CO(2) response curve to lower et(CO(2)) levels. Intravenous fentanyl on the other hand decreased CO(2) reactivity by shifting the phrenic nerve apnea threshold and the response curve to higher et(CO(2)) levels. Fentanyl effects on reactivity were partially reversed by D(1)R agonists.
Lalley
Peter M
PM
Department of Physiology, Medical Sciences Center, The University of Wisconsin, Madison, 1300 University Avenue, Madison, WI 53706, USA. pmlalley@facstaff.wisc.edu
D000200:Action Potentials / Q000187:drug effects; D000701:Analgesics, Opioid; D000704:Analysis of Variance; D000818:Animals; D001049:Apnea / Q000517:prevention & control; D002245:Carbon Dioxide / Q000494:pharmacology*; D002415:Cats; D003655:Decerebrate State; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005283:Fentanyl; D007478:Iontophoresis / Q000379:methods; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects / Q000528:radiation effects; D011930:Reaction Time; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D012684:Sensory Thresholds / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000528:radiation effects
D000701:Analgesics, Opioid; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002245:Carbon Dioxide; D005283:Fentanyl