Serotonin via presynaptic 5-HT1 receptors attenuates synaptic transmission to immature rat motoneurons in vitro.

Intracellular recordings were made from motoneurons in transverse spinal cord slices from immature (12-20 day) rats and the effects of 5-HT on dorsal root evoked excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials were assessed. With or without causing a membrane polarization, 5-HT (1-300 microM) depressed synaptic responses; the IC50 was 6 microM. The inhibitory effect was potentiated by the uptake inhibitor fluoxetine. The 5-HT1A/1B agonists 5-CT and 8-OH-DPAT and the 5-HT1B/1C agonist TFMPP reduced the synaptic responses as well, with an IC50 of 0.26, 2.2 and 0.28 microM, respectively. The synaptic depressant effect was not antagonized by methysergide (0.1-1 microM), ketanserin (1-5 microM) and MDL 72222 (1-10 microM). Methysergide alone diminished the synaptic responses in some of the motoneurons. Spiperone (1-10 microM) partially and fully antagonized the depressant effect of 5-HT and 8-OH-DPAT, but was ineffective against 5-CT and TFMPP. The 5-HT-induced synaptic depression was not accompanied by a concomitant reduction of glutamate-induced depolarizations; the latter were enhanced after repeated exposure to 5-HT in some motoneurons. Finally, 5-HT reduced the afterhyperpolarization following a single spike or a train of spikes. The results indicate that 5-HT inhibits synaptic responses in motoneurons via presynaptic 5-HT1 receptors, the activation of which reduces the liberation of excitatory and inhibitory transmitters from respective nerve endings.