Evidence for serotonin sensitivity of adult rat spinal axons: studies using randomized double pulse stimulation

We have recently shown both inhibitory and excitatory effects of serotonin on neonatal rat dorsal column axons. While neonatal rat dorsal column axons also respond to norepinephrine and GABA, adult rat dorsal columns are insensitive to the actions of both compounds. Therefore, we studied the effects of serotonin agonists on adult rat dorsal column axons using randomized double pulse stimuli at 0.2 Hz with random interpulse intervals of 3, 4, 5, 8, 10, 20, 30, 50 and 80 ms. The serotonin(1A) agonist, 8-hydroxy-dipropylaminotetralin-hydrobromide (8-OH-DPAT), significantly modulated test response amplitudes at 3, 4, 5 and 8 ms interpulse intervals by 29.6+/-4.0%, 17.4+/-2.1%, 9.6+/-2.3%, and 12.4+/-2.2% of conditioning pulse amplitudes, respectively. The mean latencies at 3, 4 and 5 ms interpulse intervals increased by 17.0+/-5.1%, 8.6+/-2.1%, and 5.1+/-1.4%, respectively (P<0.05). However, neither 10 microM 8-OH-DPAT nor 100 microM serotonin hydrochloride affected the compound action potentials evoked by conditioning or test pulses. In contrast, treatment with 100 microM quipazine dimaleate (a serotonin(2A) agonist) decreased the refractory period. While the response amplitudes to a 3-ms double pulse were reduced by 11.0+/-1.5% during the control period, the test response fell to only 2.4+/-1.8% of the conditioning response amplitudes after exposure to 100 microM quipazine. 8-OH-DPAT decreased the amplitude, prolonged the latency and increased the refractory periods of compound action potentials in the adult rat dorsal column, although a high concentration of the agonist (100 microM) was required for these effects. In contrast, the serotonin(2A) agonist, quipazine, decreased refractory periods. These results suggest that both serotonin(1A) and serotonin(2A) receptor subtypes are present on adult spinal dorsal column axons. Further, these receptors have opposing effects on axonal excitability, despite the fact that their sensitivities are relatively low.