NALOXONE-REVERSIBLE ANTINOCICEPTION BY PARACETAMOL IN RAT

Paracetamol at the dose of 400 mg/kg i.p. displayed antinociceptive ac tivity in the hot-plate test and the formalin test. Moreover, it induc ed a significant increase in brain serotonin (5-HT) concentration and a reduction in the number of 5-HT2 receptors in cortical membranes. Pr etreatment with naloxone abolished this antinociceptive activity both in the hot-plate test and in the first phase of the formalin test with out affecting the serum concentration of paracetamol. At the same time , naloxone prevented the increase in 5-HT concentration in the central nervous system and the reduction in 5-HT2 receptors in cortical membr anes. Competition experiments demonstrated that paracetamol possesses affinity for [H-3]naloxone binding sites. The action of morphine on no ciception and on the serotonergic system was similar to that of parace tamol; all morphine-induced effects were blocked by naloxone. These da ta provide further evidence for a central antinociceptive effect of pa racetamol and support the hypothesis that paracetamol exerts its antin ociceptive activity through the serotonergic system. Moreover, our res ults point to the relationship between serotonergic and opiatergic sys tems in the antinociceptive activity of paracetamol.