Cocaine and inhibition of nitric oxide synthesis produce opioid-mediated antinociception.
Cocaine and nitric oxide are known to influence the perception of pain. The present study sought to determine if the endogenous opioid peptide system participates in cocaine-induced antinociception and antinociception produced by antagonism of nitric oxide. Pain perception was measured using the hot plate test. Administration of cocaine (25 mg/kg) to male rats resulted in a significant increase in reaction time in the hot plate test, which was reversed by treatment with 3, 10, and 30 mg/kg of the opiate antagonist, naloxone. In rats that were not treated with cocaine, doses of 30 and 60 mg/kg of naloxone significantly reduced hot plate reaction Time. Treatment of animals with the nitric oxide synthase inhibitor, N omega nitro-L-arginine, produced a significant increase in response time to the hot plate, which was reversed by administration of naloxone. These data indicate that antinociception produced in the rat by cocaine appears to have a supraspinal component and to involve activation of endogenous opioid peptide activity in the brain. The results also suggest a tonic inhibition of endogenous opioid peptide activity by nitric oxide, which when antagonized, results in diminished response to pain.
Forman
L J
LJ
University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
Tringo
L
L
Sun
M
M
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004723:Endorphins / Q000502:physiology*; D004791:Enzyme Inhibitors; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004723:Endorphins; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D019335:Nitroarginine; D009270:Naloxone; D019001:Nitric Oxide Synthase; D003042:Cocaine