Actions of opioids on the dorsal root potential of the isolated spinal cord preparation of the neonate rat

Abstract

The effects of opioids were studied on the dorsal root-dorsal root evoked potential (DRP) of the neonatal hemisected spinal cord of the rat in vitro. Applications of [ d-Ala 2,Met 5]enkephalinamide (DAME), [ d-Ala 2, d-Leu 5]enkephalin (DADL), Leu 5 enkephalin. Met 5 enkephalin, Dynorphin 1–9 and normorphine produced dose-dependent depressions of the dorsal root potential. The depressant effects of these agents were antagonised by naloxone but not by the highly selective delta-opioid receptor antagonist ICI 174864. Compounds acting on the kappa opioid receptor had only weak and inconsistent inhibitory effects on the dorsal root potential. Morphine had antagonist properties on the dorsal root potential, as did the kappa agonists ethylketocyclazocine and bremazocine, but not U50488 and tifluadom. The depressant actions of opioids on the dorsal root potential thus appeared to be mediated by actions on the mu receptor type. However, only mu agonists with relatively high intrinsic activity were able to reduce the dorsal root potential. Other mu agonists, including morphine, acted as antagonists. Actions on receptors for the delta and kappa agonists, in contrast, appeared to have little influence on this response. The antagonist actions of certain kappa agonists were probably due to their high affinity for, but low efficacy at mu receptors.