Involvement of the serotonergic system in the hypoactive and antinociceptive effects of nicotine in mice.
Pretreatment with the 5-HT2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone did not reduce nicotine-induced hypomotility in mice, nor did MDL 7222, a selective 5-HT3 antagonist. In addition, 8-OH-DPAT and buspirone, 5-HT1A agonists, had no significant effects on nicotine-induced hypomotility. However, 8-OH-DPAT and buspirone did reduce the antinociceptive effects of nicotine in a dose-dependent manner. 8-OH-DPAT blockade of this nicotine effect was reversed by spiperone, a 5-HT1A/2 antagonist. Nicotine's ED50 was increased from 1.00 mg/kg (0.90-1.68) to 2.00 mg/kg (1.6-2.55) and 2.66 (1.7-3.51) by buspirone and 8-OH-DPAT, respectively. Ketanserin, spiperone and MDL 7222 had no significant effect on nicotine-induced antinociception. The present data suggest an important role of 5-HT1A receptors in the modulation of antinociceptive actions of nicotine.
Damaj
M I
MI
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Glennon
R A
RA
Martin
B R
BR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013134:Spiperone; D009538:Nicotine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D002065:Buspirone