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.
Wu
S Y
SY
Department of Pharmacology, Loyola University Stritch School of Medicine, Maywood, IL 60153.
Wang
M Y
MY
Dun
N J
NJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D005971:Glutamates; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D005473:Fluoxetine; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D018698:Glutamic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin