D1-dopamine receptor blockade slows respiratory rhythm and enhances opioid-mediated depression

Previous studies indicate that dopamine modulates the excitability of the respiratory network and its susceptibility to depression by exogenous opioids, but the roles of different subtypes of dopamine receptor in these processes are still uncertain. In this study, D1-dopamine receptor (D1R) involvement in dopaminergic modulation of respiratory rhythm and μ-opioid receptor mediated depression were investigated in pentobarbital-anesthetized cats. Intravenous administration of the D1R blocker SCH-23390 (100-200 μg/kg) slowed phrenic nerve and expiratory neuron respiratory rhythms by prolonging the inspiratory and expiratory phases. Phrenic nerve discharge intensity also increased more gradually during the inspiratory phase. SCH-23390 (150 μg/kg) also enhanced dose-dependent depression of phrenic nerve and expiratory neuron excitability, as well as rhythm disturbances, produced by the μ-opioid receptor agonist fentanyl (2-20 μg/kg, i.v.). The results suggest an important role for the D1-subtype of receptor in respiratory rhythm modulation, and indicate that this type of receptor participates in dopaminergic compensatory mechanisms directed against opioid-mediated network depression.