A μ-opioid receptor agonist DAMGO induces rapid breathing in the arterially perfused in situ preparation of rat

Ventilatory responses to opioids are complex and not yet fully understood. We evaluated concentration-dependent effects of a selective μ-opioid receptor agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) on respiratory output in the arterially perfused in situ rat preparation, which preserves the integrity of the ponto-medullary respiratory network. DAMGO (300-3400nM) was added accumulatively to the perfusate. DAMGO increased inspiratory time and diminished central vagal post-inspiratory activity. At 300-500nM DAMGO caused rapid breathing with shortening of expiratory time. The change of breathing pattern occurred within a single breath. Bilateral vagotomy did not affect the change in respiratory pattern, suggesting that it was of central origin. Additional DAMGO up to 1800nM did not affect the rapid breathing pattern, and further elevated concentrations (up to 3400nM) caused inconsistent results. Since the rapid breathing pattern was associated with the obliteration of vagal post-inspiratory activity, we conclude that DAMGO reconfigures the respiratory output to an inspiratory phase-dominant, rapidly alternating inspiration-expiration pattern.