Dynorphin1-17 reduces the inhibitory actions of mu- and delta-selective opioid agonists in cortical neurons of the rat in vivo.

Spontaneous and L-glutamate-evoked neuronal activity was recorded extracellularly from neocortical neurons of rats. Opioid agonists with preference for different receptor types were applied microiontophoretically or pneumatically from multibarrelled micropipettes. Morphine (mu-selective), [D-Ala2,D-Leu5]enkephalin (delta-selective; DADL) and the kappa-selective agonist dynorphin1-17 (DYN 17) suppressed spontaneous and evoked neuronal activity in a naloxone-reversible manner. In a substantial number of neurons the inhibitory effect of DADL and morphine was reduced or abolished by DYN 17. This antagonistic action was often observed with DYN 17 levels that did not influence the discharge activity by itself. The physiological significance of this observation remains to be elucidated.