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  • Title: Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.
    Author: Smith MA, Gordon KA, Craig CK, Bryant PA, Ferguson ME, French AM, Gray JD, McClean JM, Tetirick JC.
    Journal: Psychopharmacology (Berl); 2003 May; 167(3):265-73. PubMed ID: 12669175.
    Abstract:
    RATIONALE: 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. OBJECTIVE: The purpose of this study was to examine the interactions between cocaine and opioids possessing a range of relative efficacy at the mu receptor. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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