Serotonin and L-norepinephrine as mediators of altered excitability in neonatal rat motoneurons studied in vitro.
The actions of serotonin on the membrane properties of motoneurons and on the synaptic responses evoked by stimulating the segmental dorsal root have been investigated using intracellular recording in a neonatal rat hemisected spinal cord preparation in vitro. Superfusion with serotonin produced concentration-dependent depolarizations (EC50 32.1 microM) with an apparent increase in input resistance and increase in motoneuron excitability. During serotonin depolarizations an increase in membrane noise was seen. At higher serotonin concentrations repetitive firing was induced. Sensitivity to serotonin was enhanced by blockade of neuronal uptake with citalopram, when the EC50 was 1.4 microM. The depolarization was mimicked by alpha-methyl-5-hydroxytryptamine (EC50 11.7 microM). Serotonin depolarizations were blocked by ketanserin (0.1 and 1 microM), ritanserin (1 microM), spiperone (0.1 and 1 microM) and LY 53857 (1 microM). A norepinephrine-induced depolarization of motoneurons, which was mimicked by L-phenylephrine and antagonized by prazosin, is probably mediated by an alpha 1-adrenoceptor. An inhibitory action of serotonin was also apparent. The frequency and amplitude of spontaneous postsynaptic potentials and the response following dorsal root stimulation were markedly reduced. This action was mimicked by 5-carboxamidotryptamine and 8-hydroxy-2-(n-dipropylamino)tetralin, but was not antagonized by ketanserin (1 microM), ritanserin (1 microM), methiothepin (1 microM), metergoline (1 microM), spiperone (1-10 microM) or 21-009 (1-10 microM). It is proposed that the depolarization and increase in excitability of spinal motoneurons is mediated by a serotonin (5-HT2) receptor subtype.
Elliott
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P
Department of Physiology, University of Wales College of Cardiff, U.K.
Wallis
D I
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D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008566:Membranes / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D009638:Norepinephrine