Modulation of cocaine-induced antinociception by opioid-receptor agonists

Pharmacol Biochem Behav. 1999 Feb;62(2):247-53. doi: 10.1016/s0091-3057(98)00161-0.


Cocaine can produce antinociception in a number of animal models. The present experiments were designed to determine if opioid receptor agonists modulate cocaine-induced antinociception in rats. Cocaine produced a dose-dependent increase in antinociception in the hot-plate, but not paw-pressure, test. The combination of cocaine and morphine or [D-Pen2, D-Pen5]enkephalin (DPDPE) produced results no greater than simple additivity in the hot-plate test. However, the combination of cocaine and morphine produced greater antinociception than morphine alone in the paw-pressure test. A low dose of U69,593 potentiated the effects of cocaine in the hot-plate test. In contrast, cocaine attenuated the effect of U69,593 in the paw-pressure test. Both naltrexone and the selective kappa-opioid receptor antagonist nor-binaltorphamine (nor-BNI) blocked the potentiation of cocaine-induced antinociception by U69,593. The combination of U69,593 and cocaine can produce superadditive or subadditive effects, depending upon the doses and antinociceptive assay used.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Benzeneacetamides*
  • Cocaine / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / pharmacology
  • Male
  • Morphine / pharmacology
  • Pain Measurement
  • Pain*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / agonists*
  • Receptors, Opioid, kappa / agonists


  • Analgesics
  • Benzeneacetamides
  • Enkephalins
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Morphine
  • Enkephalin, D-Penicillamine (2,5)-
  • Cocaine
  • U 69593