Excitatory and inhibitory effects of serotonin on spinal axons

We studied the effects of serotonin on compound action potentials in dorsal columns isolated from young (nine to 13 days old) rats. Conducting action potentials were activated by submaximal (50%) and supramaximal constant current electrical stimuli and recorded with glass micropipettes. At 10 microM and 100 microM concentrations, serotonin significantly increased mean action potential amplitudes by 9.6 +/- 6.5% (+/- S.D., P < 0.05) and 16.6 +/- 12.2% (+/- S.D., P < 0.005), respectively. Likewise, 10 microM and 100 microM of quipazine (a serotonin2A agonist) increased the amplitudes by 9.6 +/- 2.5% (+/- S.D., P < 0.0005) and 37.7 +/- 8.7% (+/- S.D., P < 0.0005), respectively. In contrast, 10 microM and 100 microM concentrations of 8-hydroxy-dipropylaminotetralin-hydrobromide (a serotonin 1A agonist) reduced axonal excitability by -9.4 +/- 5.5% (+/- S.D., P < 0.05) and -32.9 +/- 10.6% (+/- S.D., P < 0.0005), respectively. At 50 microM concentration, mianserin (a serotonin2A and serotonin2C antagonist) eliminated the excitatory effects of 100 microM quipazine dimaleate. The combination of 50 microM mianserin and 100 microM serotonin reduced action potential amplitudes by -5.6 +/- 4.9% (+/- S.D., P < 0.05). These results suggest that serotonin1A and serotonin2A receptor subtypes are present on spinal dorsal column axons. These two receptor subtypes have opposing effects on axonal excitability. The ratios and sensitivities of these two axonal receptor subtypes may modulate axonal excitability in rat dorsal column axons and have important implications for both development and injury of axons.