Dopamine1 receptor agonists reverse opioid respiratory network depression, increase CO2 reactivity

Department of Physiology, Medical Sciences Center, The University of Wisconsin, Madison, 1300 University Avenue, Madison, WI 53706, USA.
Respiratory Physiology & Neurobiology (Impact Factor: 1.97). 03/2004; 139(3):247-62. DOI: 10.1016/j.resp.2003.10.007
Source: PubMed

ABSTRACT 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.

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    • "There is some evidence of a continuous modulation of the preBötC by histamine and dopamine. Thus, the histamine-type-1-receptor antagonist, pyrilamine, reduces the en bloc respiratory frequency and attenuates respiratory depression in hypoxia in mice (Dutschmann et al., 2003), while the dopamine-type-1-receptor antagonist SCH-23390 slows the respiratory rhythm of cats in vivo (Lalley, 2004, 2005). "
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    • "Few studies have investigated the role of D1 receptors on the ventilatory response to hypercapnia. Lalley (Lalley, 2004) examined the role of D1 receptors on ventilation in anesthetized and unaesthetized decerbrate cats and noted that D1 receptor agonists given intravenously stimulated frequency of breathing of cats in air and during exposure to CO 2 . "
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