Opposite effects of the delta- and mu-opioid receptor agonists on ventilation in conscious adult dogs

We studied ventilation and ventilatory pattern in adult unanesthetized dogs after intracisternal administration of morphiceptin analogue (MA) (Tyr-Pro-NMePhe-D-Pro-NH2) and morphine sulfate (MS) which are mu-receptor opioid agonists and after D-Ala-D-Leu-enkephalin (DADLE), a preferential delta-receptor opioid agonist. DADLE induced a prolongation in expiratory time, Te, and a reduction in instantaneous minute ventilation, Vt/Ttot, which lasted for about 2 h and was dose dependent. In contrast, MA and MS induced a striking decrease in Te and tidal volume with a net increase in Vt/Ttot. Both MA and DADLE increased the number of sighs per unit time while morphine did not. Naloxone increased Vt/Ttot when used after both DADLE or MA but larger doses were required for an observable effect after DADLE than after MA. These data suggest that in the unanesthetized dog: (1) the effect of intracisternal opioids on ventilation and ventilatory pattern is not uniform and (2) the opioid mu-receptor subsystem may involve different neuronal pathways from those of the opioid delta-receptor subsystem to modulate breathing.