Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes.
Male Wistar rats were treated with ondansetron (1 and 2 mg/kg s.c.), ketanserin (0.2, 1 and 5 mg/kg s.c.) or NAN-190 (1, 3 and 5 mg/kg i.p.) 15 min before acetylsalicylic acid (ASA, 400 mg/kg i.p.), and 30 min thereafter the pain threshold was evaluated. The antinociceptive activity of ASA in the hot-plate test was variously affected by ondansetron, ketanserin and NAN-190: at the highest dose (2 mg/kg s.c.) ondansetron abolished it while ketanserin (5 mg/kg s.c.) significantly reduced it, and NAN-190 (1-5 mg/kg) did not significantly modify the effect of ASA. Binding experiments indicate that both ondansetron and ketanserin completely prevented the decrease in the maximum number of 5-HT(2) receptors (B(max)) provoked by ASA. These data indicate that the central antinociceptive activity of ASA is modulated in a different manner by serotonin receptor antagonists, and that 5-HT(2) and 5-HT(3) receptors may exert a pivotal role in nociception, alone or in association.
Department of Biomedical Science, Section of Pharmacology, Department of Internal Medicine, University of Modena, Italy. Sandrini,Maurizio@unimo.it
Maurizio
M
Sandrini
Giovanni
G
Vitale
Luigy Alberto
LA
Pini
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D017294:Ondansetron; D007650:Ketanserin; D001241:Aspirin