Modulation of cocaine-induced antinociception by opioid-receptor agonists.
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.
Waddell
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Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Holtzman
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SG
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain; D010147:Pain Measurement; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists