Cocaine-like discriminative stimulus effects and [3H]dopamine uptake inhibition produced by selected partial opioid agonists

Partial opioid agonists can produce their actions at opioid as well as some non-opioid sites. Although the receptor systems underlying these non-opioid effects are not completely clear, recent studies indicate the possible involvement of activity at the dopamine uptake site. One purpose of the present investigation was to examine the ability of selected partial opioid agonists (dezocine, meperidine and [+]-propoxyphene) with non-opioid actions to produce cocaine-like stimulus effects. Because non-opioid effects can be apparent under conditions in which opioid-mediated effects are blocked or at doses that markedly decrease responding, these opioids were also examined in combination with the opioid antagonist naltrexone. A second purpose was to determine the ability of these opioids to inhibit [H-3] dopamine uptake in rat caudate putamen. Cocaine and the direct-acting dopamine agonist (-)-quinpirole, but not (+)-propoxyphene, butorphanol, morphine, U50,488 and pentobarbital, substituted completely for the cocaine stimulus. Dezocine substituted for the cocaine stimulus in the majority of the rats tested only when administered in combination with naltrexone. Meperidine also substituted for the cocaine stimulus in the majority of the rats tested, although this pattern of substitution was not consistently altered by naltrexone. Dezocine and meperidine inhibited [H-3] dopamine uptake in a manner consistent with that produced by cocaine. The results suggest that dezocine and meperidine can produce cocaine-like stimulus effects and that these effects are likely mediated by activity at the dopamine uptake site. (C) 2001 Lippincott Williams & Wilkins.