Effect of Dextromethorphan on Antinociception and Tolerance Induced by Swim-Stress in the Formalin Test

Background: In the present study, the effect of dextromethorphan on antinociception and tolerance induced by water swim-stress in the formalin test was investigated. Methods: Swim- stress at 8ºC induces antinociception in both phases of the formalin test. Intraperitoneal administration of dextromethorphan (60 mg/kg) also induces antinociception in the second phase of the formalin test. The lower doses of dextromethorphan (1.25, 2.5, and 5 mg/kg) which did not induce antinociception alone, but did so in combination with swim- stress (40 second), showed antinociceptive effect in both phases of the test. Exposure to water swimming stress with a period of 20 sec, once daily for three days, altered swim- stress- induced antinociception in the formalin test, when tested on the fourth day. Results: In these animals, exposure to either water swimming stress alone or water swimming stress in combination with dextromethorphan showed potentiation of antinociception induced by swim- stress up to 20 second and decreased the response induced by 40 and 60 second swimstress, indicating a tolerance induction. Dextromethorphan (20 mg/kg) did not alter the changes induced by three days exposure to swim- stress. Conclusion: The results may indicate a possible involvement of n-methyl-d-aspartate receptor mechanism in the antinociception but not tolerance induced by swim- stress at 8ºC.