Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.

Abstract

Cocaine and mu opioid agonists increase central dopamine concentrations and produce robust interactions at both neurochemical and behavioral levels. Although the interactions between cocaine and high-efficacy mu opioids have been well characterized, the interactions between cocaine and lower efficacy opioids have not been as extensively examined. The purpose of this study was to examine the interactions between cocaine and opioids possessing a range of relative efficacy at the mu receptor. Male, Long-Evans rats were habituated to an open-field, locomotor activity chamber, and the effects of cocaine and various opioids were tested under a cumulative dosing procedure. In this procedure, a selected dose of an opioid was administered during the first component of a session, with increasing doses of cocaine administered during subsequent components. When administered alone, cocaine produced dose-dependent increases in locomotor activity that was stable across 5 weeks of behavioral testing. The high-efficacy mu opioid levorphanol, and the low-efficacy opioids buprenorphine, butorphanol, nalbuphine and (-)-pentazocine, dose-dependently enhanced the effects of cocaine at doses that did not alter locomotor activity when administered alone. In contrast, the opioid antagonist naloxone, and to a lesser extent, the kappa opioid spiradoline attenuated the effects of cocaine at doses that did not alter locomotor activity when administered alone. Across an extensive dose range, the low-efficacy opioid nalorphine failed to alter cocaine's locomotor-activating effects. These data suggest that low-efficacy opioids possessing significant mu-agonist activity (e.g. buprenorphine, butorphanol, nalbuphine, (-)-pentazocine) may potentiate the effects of cocaine in a manner similar to that typically observed with high-efficacy mu opioids.