Opposing effects on the phrenic motor pathway attributed to dopamine-D1 and -D3/D2 receptor activation

Peter M. Lalley, Steve W. Mifflin

Research output: Contribution to journalArticle

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Abstract

Previous in vivo studies revealed that dopamine-D1-agonists elevate excitability of ventral respiratory column (VRC) neurons and increase discharge activity in the phrenic motor output through actions in the brainstem. In this in vivo study performed on pentobarbital-anesthetized cats, we show that D1-agonists (SKF-38393, dihydrexidine) given intravenously enhanced discharge activity in VRC inspiratory neurons and the phrenic nerve in two stages; discharge intensity first increased to a peak and then discharge duration increased. Cross-correlation analysis of VRC inspiratory neuron and phrenic nerve discharges showed that both stages increased strength of coupling between medullary inspiratory neurons and the phrenic motoneuron output. Intracellular recording and microiontophoresis experiments indicated that D1-agonists produced their stimulatory effects indirectly through actions on synaptic inputs to VRC inspiratory neurons. Because other laboratories have provided evidence that dopamine acting on other types of receptors depresses respiratory neuron excitability we tested the effects of piribedil, an agonist that activates receptors of the generally depressant D3/D2-dopamine receptor family, on phrenic nerve activity. Piribedil depressed phrenic nerve inspiratory discharge intensity, prolonged discharge duration, slowed burst frequency and slowed rate of action potential augmentation. The effects of piribedil were partially counteracted by intravenous injection of dihydrexidine. We propose that under normal, steady state conditions, D1-receptor-mediated excitatory modulation of phrenic motor output overrides D3/D2-receptor mediated inhibition.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalRespiratory Physiology and Neurobiology
Volume181
Issue number2
DOIs
Publication statusPublished - 30 Apr 2012

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Keywords

  • Brainstem respiratory network
  • Dopamine
  • Dopamine receptor
  • Inspiratory neuron
  • Phrenic motor pathway

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