Excitatory and inhibitory effects of opioid agonists on respiratory motor output produced by isolated brainstems from adult turtles (Trachemys)

To determine how central opioid receptor activation alters turtle breathing, respiratory-related hypoglossal (XII) motor bursts were recorded from isolated adult turtle brainstems during 60 min bath applications of agonists for delta- (DOR), kappa- (KOR), or nociceptin/orphanin (NOR) receptors. DADLE (DOR agonist) abolished XII burst frequency at 0.3-0.5 μM. DPDPE (DOR agonist) increased frequency by 40-44% at 0.01-0.1 μM and decreased frequency by 88 ± 8% at 1.0 μM. U-50488 and U-59693 (KOR agonists) decreased frequency by 65-68% at 100 and 50 μM, respectively. Orphanin (NOR agonist) decreased frequency by 31-51% at 1.0-2.0 μM during the first 30 min period. Orphanin (0.5 and 2.0 μM) increased bursts/episode. Although morphine (10 μM) abolished frequency in nearly all brainstems, subsequent co-application of phenylephrine (α1-adrenergic agonist, 20-100 μM) with morphine restored activity to 16-78% of baseline frequency. Thus, DOR, KOR, and NOR activation regulates frequency and NOR activation regulates episodicity, while α1-adrenergic receptor activation reverses opioid-induced respiratory depression in turtles.