OPIOID CONTROL OF THE SPINAL RELEASE OF CHOLECYSTOKININ (CCK) IN MORPHINE-TOLERANT AND NONTOLERANT RATS

The K+-evoked release of cholecystokinin (CCK)-like material (CCKLM) f rom spinal cord slices of naive or placebo-treated rats was found to b e under complex opioid control (inhibited by the activation of mu or o ne subtype of partial derivative receptors, and enhanced by the activa tion of another partial derivative receptor subtype), while the releas e from morphine-tolerant rats was only under the stimulatory influence of a partial derivative-dependent mechanism. Morphine itself exerted a biphasic effect (inhibitory at low concentrations through the activa tion of mu receptors, and stimulatory at a high concentration, 10 mu M , through the activation of partial derivative receptors) on spinal CC KLM release in control (naive or placebo-treated) rats, and only a sti mulatory effect (at 10 mu M) in morphine-tolerant rats. These data ind icate that in morphine-tolerant rats opioids retain only their excitat ory influence on spinal CCK-containing neurons, in line with the hypot hesis that CCK release may be enhanced by chronic morphine treatment.