Differential involvement of central 5-HT1B and 5-HT3 receptor subtypes in the antinociceptive effect of paracetamol.
OBJECTIVE
We investigated the effect of pre-treatment with ondansetron or CP 93129 (a 5-HT1B agonist) on the antinociceptive activity of paracetamol and the changes in central 5-HT3 receptors induced by paracetamol alone or co-administered with ondansetron.


METHODS
Male Wistar rats (eight per group) were injected with ondansetron (2 and 4 mg/kg s.c.) or CP 93129 (0.5, 1 and 2 mg/kg s.c.) 15 min before paracetamol (400 mg/kg, i.p.).


METHODS
Pain threshold was evaluated in the hot-plate or in the paw pressure test 30 min after the last treatment. 5-HT3 receptor binding capacity was measured in the frontal cortex, temporal-parietal cortex and midbrain by means of radioligand binding technique. Statistical analysis was done using ANOVA followed by Student-Newman-Keuls test and 2X2 factorial analysis when appropriate.


RESULTS
Pre-treatment with ondansetron, at doses of 2 and 4 mg/kg, did not affect the antinociceptive activity of paracetamol in the hot-plate test and in the paw pressure test. Paracetamol did not change the characteristics of 5-HT3 receptors in all the areas investigated. Ondansetron (4 mg/kg s.c.) per se significantly increased the 5-HT3 receptor number in the areas used, the effect not being modified by co-administration with paracetamol. On the other hand, CP 93129 (2 mg/kg s.c.) significantly prevented the effect of paracetamol in both algesimetric tests used.


CONCLUSIONS
Our data indicate that 5-HT1B but not 5-HT3 receptors are involved in the antinociceptive effect of paracetamol in our experimental conditions.
D000082:Acetaminophen / Q000378:metabolism / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010147:Pain Measurement; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D020033:Protein Isoforms; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D044406:Receptors, Serotonin, 5-HT3; D058825:Serotonin 5-HT1 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D000082:Acetaminophen; D017294:Ondansetron