Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord

Holohean, Alice M.; Hackman, J.C.; Shope, S.B.; Davidoff, Robert A.

doi:10.1016/0006-8993(92)90736-s

Cited by 13 publications

(10 citation statements)

References 39 publications

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“…NMDA channels and 5HT receptors are integral in the regulation of spinal reflexes and rhythmic motor pathways (13,14,(75)(76)(77). Activation of 5HT2C receptors induces long lasting reflexes (78), and after spinal cord injury, locomotion in rats requires constitutive activity of 5HT2C receptors (79).…”

Section: Discussionmentioning

confidence: 99%

“…Serotonin (5-hydroxytryptamine; 5HT) is a major neuromodulator of NMDA-mediated motoneuron output (12)(13)(14)(15). Spinal motoneurons express a variety of 5HT receptor subtypes (16 -20) that are activated by 5HT released from tracts descending from the raphe nuclei (21) and also by 5HT circulating extrasynaptically (22).…”

Section: Nmdamentioning

confidence: 99%

“…There are 7 classes of 5HT receptors with 1, 2, and 4 -7 classes that are generally considered to be G-proteincoupled receptors; the exception, 5HT3, forms an ion channel. NMDA-mediated motoneuronal activity has been shown to be depressed by the activation of 5HT2A and facilitated by 5HT1A and 5HT2B receptor subtypes (12)(13)(14)(15). The role of NMDA sub-units in 5HT-mediated modulation of NMDA-induced motoneuronal depolarization has not been explored.…”

Section: Nmdamentioning

confidence: 99%

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5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Bigford

Chaudhry

Keane

et al. 2012

Journal of Biological Chemistry

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Background: 5-Hydroxytryptamine (5HT) modulates N-methyl-D-aspartate (NMDA) depolarization. Results: 5HT2C co-immunoprecipitates with GluN2A and enhances NMDA motoneuronal depolarization through phosphorylation of Src . Conclusion: 5HT modulates NMDA through Src phosphorylation in a molecular complex that is localized in the processes of spinal neurons. Significance: 5HT2C modulation of NMDA excitation is coordinated by a molecular complex.

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Section: Discussionmentioning

confidence: 99%

Section: Nmdamentioning

confidence: 99%

Section: Nmdamentioning

confidence: 99%

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5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Bigford

Chaudhry

Keane

et al. 2012

Journal of Biological Chemistry

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“…In frog spinal cord, different results have been obtained according to the receptor-specificity of the 5-HT agonist used. Whereas low ventral root potentials and postsynaptic responses to NMDA and kainate in the presence of TTX (Holohean et al, 1992b). The recent demonstration that 5-HT and glutamate are coreleased by single raphe neurones (Johnson, 1994) further stimulates this research area.…”

Section: Introductionmentioning

confidence: 94%

“…In (Holohean et al, 1992a), high concentrations of 5-HT (> 10 giM) reduced both synaptic 1 Author for correspondence. 2Present address: UPR 9011, Neurobiologie et Mouvements,31 ventral root potentials and postsynaptic responses to NMDA and kainate in the presence of TTX (Holohean et al, 1992b). The recent demonstration that 5-HT and glutamate are coreleased by single raphe neurones (Johnson, 1994) further stimulates this research area.…”

Section: Introductionmentioning

confidence: 99%

Voltage‐dependent block of NMDA responses by 5‐HT agonists in ventral spinal cord neurones

Chesnoy-Marchais

Barthe

1996

British J Pharmacology

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1 Modulation by 5-hydroxytryptamine receptor agonists of the NMDA responses of ventral spinal cord neurones was studied by use of the whole-cell patch-clamp technique. 2 In a Mg-free solution containing tetrodotoxin and glycine, 5-hydroxytryptamine (5-HT, 10-100 ,UM) reduced the NMDA response, the block increasing with hyperpolarization. Kainate responses were little affected. 3 Some classical agonists of 5-HT receptors induced similar blocking effects. At 10 IM, both a selective agonist of 5-HT2 receptors, (±)-2,5-dimethoxy-4 iodo amphetamine (DOI), and a selective agonist of some 5-HTI receptors, (±)-8-hydroxy-2(n-dipropyl amino) tetralin (8-OH-DPAT), induced pronounced blocking effects, of 48% and 33% respectively at -100 mV, whereas another 5-HT1 agonist, 5-carboxamidotryptamine (5-CT) was ineffective. At 100 gIM, 5-methoxytryptamine (5-MeOT) induced a complete block of the NMDA responses recorded at -100 mV. The order of potency was: 5-MeOT DOI> 8-OH-DPAT > 5-HT > 5-CT. 4 Neither spiperone nor ketanserin (1 riM) prevented the blocking effect of 5-HT or DOI. 5 Prolonged preincubations with 5-HT did not block the response if NMDA was applied without 5-HT. When 5-HT agonists were applied both by preincubation and with NMDA, the degree of block increased during the NMDA application.6 Lowering the NMDA concentration (from 100 to 20 giM) slightly decreased the blocking effect of 5-MeOT. 7 External Mg2+ ions (1 mM) also reduced the blocking effects of 5-HT and 5-MeOT. 8 The blocking effects described appear to be independent of classical 5-HT receptors. Their voltagedependence suggests a mechanism of open channel block consistent with all the results obtained.

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Serotonin depletion by 5,7-dihydroxytryptamine alters deutocerebral development in the lobster,Homarus americanus

et al. 1997

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The olfactory and accessory lobes constitute prominent histological structures within the larval and mature lobster deutocerebrum, and both are associated with a dense innervation from paired serotonergic nerve cells, the dorsal giant neurons (DGNs). During development, the cell bodies of the DGNs are the first central somata to express serotonin (5‐HT), and the onset of their 5‐HT immunoreactivity coincides with the beginning of accessory lobe formation. In contrast, the olfactory lobe anlagen emerge much earlier and grow in the apparent absence of serotonin. The role of serotonergic input for the development of these brain structures was investigated in lobster embryos after serotonin had been depleted pharmacologically with the neurotoxin 5,7‐dihydroxytryptamine. A ∼90% reduction of serotonin was confirmed in eggs using high‐performance liquid chromatography with electrochemical detection. Morphometric analyses suggested that serotonin depletion dramatically slowed the growth of olfactory and accessory lobes, although glomeruli differentiated at the normal time in both areas. The toxin exhibited a high degree of specificity for serotonergic neurons and associated target regions, and serotonin depletion persisted for at least 2 months following treatment. The goal of future experiments is to determine which of the cell types that innervate the olfactory and accessory lobes are affected by toxin treatment, thereby resulting in the retarded growth of these areas. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 357–373, 1997

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Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord

Cited by 13 publications

References 39 publications

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Voltage‐dependent block of NMDA responses by 5‐HT agonists in ventral spinal cord neurones

Serotonin depletion by 5,7-dihydroxytryptamine alters deutocerebral development in the lobster,Homarus americanus

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