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 pepti de system participates in cocaine-induced antinociception and antinoci ception produced by antagonism of nitric oxide. Pain perception was me asured using the hot plate test. Administration of cocaine (25 mg/kg) to male rats resulted in a significant increase in reaction time in th e hot plate test, which was reversed by treatment with 3, 10, and 30 m g/kg of the opiate antagonist, naloxone. In rats that were not treated with cocaine, doses of 30 and 60 mg/kg of naloxone significantly redu ced hot plate reaction time. Treatment of animals with the nitric oxid e synthase inhibitor, N(omega)nitro-L-arginine, produced a significant increase in response time to the hot plate, which was reversed by adm inistration of naloxone. These data indicate that antinociception prod uced in the rat by cocaine appears to have a supraspinal component and to involve activation of endogenous opioid peptide activity in the br ain, The results also suggest a tonic inhibition of endogenous opioid peptide activity by nitric oxide, which when antagonized, results in d iminished response to pain. (C) 1997 Elsevier Science Inc.