Serotonin receptor subtypes in spinal antinociception in the rat

The aim of the present study was to clarify the subtypes of serotonin (5-HT) receptors involved in spinal antinociception in the rat. 1) Intrathecal (i.t.) injection of 5-HT (25-200 micrograms) produced a dose-dependent increase in tail-flick latency. 2) Intrathecal injection of fluoxetine, a 5-HT uptake blocker (25-40 micrograms), resulted in a bell-shaped dose-related antinociception with peak effects occurring at 10 micrograms. 3) A bell-shaped antinociceptive effect was obtained by i.t. injection of the 5-HT1A agonist (+)-hydroxy-2-(di-N-propylamino)tetralin (0.25-2 micrograms), with the maximal effect occurring at 0.5 micrograms, which can be prevented by the 5-HT1A antagonist spiperone (25 micrograms i.t.). 4) A similar dose-response curve was obtained following the i.t. injection of the 5-HT1B agonist 1-[3-(trifluoromethyl)phenyl]-piperazine maleate (1-125 micrograms) with the maximal effect observed at 25 micrograms. 5) Neither the 5-HT2 agonist (+/-)-alpha-methyl-5-HT-maleate nor the 5-HT3 agonist (+/-)-2-methyl-5-HT-maleate produced significant antinociceptive effects at doses up to 50 micrograms. Spontaneous tail-flicks emerged at doses higher than 50 micrograms. 6) The antinociceptive effect induced by 5-HT (200 micrograms i.t.) could be attenuated dose-dependently either by the 5-HT1A antagonist spiperone (5 and 25 micrograms i.t.) or by the 5-HT1C/2 antagonist mianserin (0.5-50 micrograms i.t.), but not by the 5-HT2 antagonist 1-(1-naphthyl)piperazine hydrochloride or the 5-HT3 antagonist 3-tropanyl-indole-3-carboxylate.(ABSTRACT TRUNCATED AT 250 WORDS)