SELECTIVE DEPRESSION OF DORSAL ROOT-EVOKED HIGH-THRESHOLD SYNAPTIC EXCITATION BY THE SELECTIVE KAPPA-OPIOID RECEPTOR AGONIST ENADOLINE IN THE NEONATAL RAT HEMISECTED SPINAL-CORD IN-VITRO

The present study aimed to compare the actions of the selective ic opi oid receptor agonist enadoline (CI-977) with morphine in order to see if there is a heterogeneity of opioid receptors between spinal reflex pathways. High (C- and A-fibre evoked activity) and low (A-fibres only ) intensity electrical stimulation of dorsal roots in the neonatal rat hemisected spinal cord preparation in vitro was used to distinguish b etween synaptic activity measured in the corresponding ventral root. E nadoline selectively depressed the high intensity-evoked EPSP with an EC50 of 7.6 nM (n = 7), contrasting with our previous finding: in this preparation that morphine is an equipotent depressant of A- and C-fib re-mediated synaptic responses. The depressant effects of enadoline an d morphine were reversed by naloxone giving apparent K-d values of 14 +/- 3 nM (n = 4) for enadoline-induced and 4.2 +/- 1 nM (n = 4) for mo rphine-induced depression. These data suggest that activation of kappa opioid receptors has a selective depressant action on C-fibre-mediate d synaptic activity. Such a functional difference mediated at a subcla ss of opioid receptors has not been previously observed in an in vitro spinal preparation. (C) 1998 Elsevier Science Ltd. All rights reserve d.