5-HT1B but not 5-HT6 or 5-HT7 receptors mediate depression of spinal nociceptive reflexes in vitro

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Abstract
1. The identity of the serotonin (5-HT) receptors modulating the transmission of segmental C-fibre mediated signals was studied using an in vitro preparation of the hemisected spinal cord from rat pups. 2. Responses to trains of stimuli delivered to a lumbar dorsal root were recorded from the corresponding ventral root. The resulting cumulative depolarization (CD) mediated by unmyelinated fibres was quantified in terms of integrated area. The amplitude of the mono-synaptic reflex was also measured. Serotonergic agents were superfused at known concentrations and their effects on the reflexes evaluated. 3. 5-HT had depressant effects on the CD (EC(50) 34 microM). The rank order of potency of agonists for the depression of the CD was 5-carboxamidotryptamine (5-CT)>alpha-methylserotonin (alpha-met-5-HT) approximately 5-HT>42-methylserotonin (2-met-5-HT)approximately 8-OH-DPAT. 4. All the agonists including 2-met-5-HT and 8-OH-DPAT had strong depressant effects on the mono-synaptic reflex with the following order of potency: 5-CT>48-OH-DPAT>4alpha-met-5-HT approximate5-HTapproximate2-met-5-HT. 5. The inhibitory effects of 5-HT, alpha-met-5-HT and 5-CT were attenuated by the non-specific 5-HT antagonist methiothepin (1 microM) and by the 5-HT(1A/1B) antagonist SDZ 21009 (100 nM) but not by the selective 5-HT(1A) antagonist WAY 100135 (1 microM). 6. Other antagonists known to block 5-HT(2), 5-HT(6) and/or 5-HT(7) receptors (ketanserin, RO 04-6790, ritanserin and clozapine) did not change the effect of the agonists. 7. The data suggest an important contribution of 5-HT(1B) receptors to the inhibition of spinal C-fibre mediated nociceptive reflexes but no experimental support was found for the intervention of 5-HT(2), 5-HT(6) or 5-HT(7) receptors in this in vitro model.