Self-administration of ketocyclazocine and ethylketocyclazocine by the rat

Abstract

The purpose of the study was to assess possible substitution of either ketocyclazocine or ethylketocyclazocine for morphine in rats maintaining their own dependence by self-administration. Rats were prepared with indwelling IV cannulae, made tolerant to and physically dependent on morphine, then trained to lever press for morphine self-injections on a fixed ratio (FR) schedule of reinforcement. When either ketocyclazocine or ethylketocyclazocine was substituted for morphine, rats self-administered single injections of these kappa opioid agonists at relatively evenly spaced intervals over a 24-hr period. These self-injection patterns continued for up to at least 15 consecutive days. Substitution of saline for the kappa opioid agonists did not result in the emergence of a morphine-like abstinence syndrome. Differences in extent and intensity of withdrawal between morphine and these kappa opioid agonists indicate the involvement of separate receptor populations in the process of dependence on morphine and these kappa opioid agonists.