Serotonin andl-norepinephrine as mediators of altered excitability in neonatal rat motoneurons studied in vitro

Elliott, Peter J.; Wallis, David

doi:10.1016/0306-4522(92)90163-v

Cited by 109 publications

(74 citation statements)

References 41 publications

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“…Further, the rank order of potency for MN depolarization (5-HT>a-methyl-5-hydroxytryptamine (a-Me-5-HT) > 5-CT> 5-methoxytryptamine (5-MeOT) > > 8-OH-DPAT, sumatriptan, methysergide, Wallis et al, 1991) is very different from the rank order for reflex depression (5-CT > sumatriptan > methysergide > 5-HT > 8-OH-DPA-T > 5-MeOT > a-Me-5-HT, Crick et al, 1994). Nevertheless, the EC50 for 5-HT depolarization is 1.4 gM (Elliott & Wallis, 1992), while the IC50 for 5-HT depression of MSR is 30 nM (Crick & Wallis, 1991).…”

Section: Discussionmentioning

confidence: 87%

“…The longlasting inhibition of MSR evoked on stimulation of lateroventral descending pathways to the ventral horn (Miyata et al, 1987;Yomono et al, 1992) is reportedly due to 5-HT acting at 5-HT2N2c receptors (Yomono et al, 1992;Wallis et al, 1993a,b), despite the presence on motoneurones of 5-HT2A receptors increasing cell excitability (Jackson & White, 1990;Wang & Dun, 1990;Elliott & Wallis, 1992). The antagonists which block this endogenous 5-HT-mediated inhibition (ketanserin, ritanserin, spiperone, methiothepin and yohimbine) would be capable of blocking 5-HTlD-like receptors (Table 2) at the concentrations used (usually 1 yM).…”

Section: Actions Of 5-htmentioning

confidence: 99%

“…Crick et al (1994) proposed that an avid uptake mechanism for 5-HT effectively protects synaptic 5-HT receptors from exogenous 5-HT but does not prevent released 5-HT, which presumably transiently reaches much higher concentrations, from activating ketanserin-sensitive receptors. At higher concentrations, 5-HT directly depolarizes spinal motoneurones (EC" 1.4 yM in the presence of citalopram, Elliott & Wallis, 1992) via an action at 5-HT2 receptors (Wang & Dun, 1990). On certain motoneurones a second 5-HT receptor with a distinct pharmacology which mediates depolarization may also be involved (Larkman & Kelly, 1991;.…”

Section: Introductionmentioning

confidence: 99%

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Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Manuel¹,

Wallis²,

Crick³

1995

British J Pharmacology

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1 The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and R( + )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and also by the selective 5-HTlD agonists, sumatriptan and N-methyl-3-(1-methyl-1-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548).2 Ketanserin (1 gM) and methiothepin (1 gM) reduced the duration of depressions elicited by 5-CT, but not those produced by 5-HT, sumatriptan, GR 85548, methysergide or 8-OH-DPAT.3 The IC50 for MSR depression by 5-CT was 3.6, 2.1 -6.2nM (n=4), by sumatriptan was 15.2, 12.9-18.0nM (n=32), by GR 85548 was 18.4, 11.7-29.1 nM (n =12), by methysergide was 29.8, 10.2-87.1nM (n=4) and by 8-OH-DPAT was 0.21, 0.11-0.43 MM (n=3) (geometric means and 95% confidence limits). 4 Ketanserin (0.1 or 1 UM) antagonized competitively responses to sumatriptan (apparent pA2 7.8 ± 0.1, n = 5), GR 85548 (apparent pA2 7.6, unpaired data, n = 5), methysergide (apparent pA2 7.9 ± 0.12, n=4) and 8-OH-DPAT (apparent pA2 8.3 ± 0.1, n= 3). Concentration-response curves to 5-CT showed a smaller, parallel shift to the right (apparent pA2 6.8 ± 0.1, n = 4), but responses to 5-HT were unaffected by ketanserin (1 gM) (n = 4). Neither with these concentrations nor with concentrations in the range 1-3 nm was there any unequivocal blockade of responses to sumatriptan. 9 It is concluded that sumatriptan, GR 85548, methysergide and 8-OH-DPAT depress the MSR in the neonate rat spinal cord via ketanserin-sensitive receptors, which have some similarities to 5-HTLIT1 receptors but which are not blocked by GR 127935. 5-HT released by tryptaminergic pathways may act via the same receptors to depress the MSR. 5-HT applied to the cord probably acts via a different, possibly novel 5-HT receptor to depress the MSR.

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Section: Discussionmentioning

confidence: 87%

Section: Actions Of 5-htmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Manuel¹,

Wallis²,

Crick³

1995

British J Pharmacology

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“…The effects of serotonin or serotonergic agents on spinal cord locomotor output have been studied in various models ranging from in vitro postnatal spinal cord preparations to kinematic analysis in freely moving adult animals (Antri, et al, 2002, Cazalets, et al, 1995. In particular, 5-HT 2 R agonists have received a lot of attention due to their ability to increase the excitability of motoneurons (Barasi and Roberts, 1974, Elliott and Wallis, 1992, Machacek, et al, 2001. The 5-HT 2 R agonists, quipazine and m-CPP, have been shown to significantly improve treadmill-trained locomotion after complete transection in rats (Antri, et al, 2002, Kim, et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Lee

Johnson

Wrathall

2007

Experimental Neurology

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The amplitude of the H-reflex increases chronically after incomplete SCI and is associated with the development of exaggerated hindlimb reflexes. Although the mechanism for this increased H-reflex is not clear, previous studies have shown that pharmacological activation of the 5-HT 2 receptors (5-HT 2 R) can potentiate the monosynaptic reflex. This study tested the hypothesis that increased expression of 5-HT 2 R on motoneurons is involved in increased H-reflex amplitude after a standardized clinically-relevant contusive SCI. Adult female rats were subjected to contusion, complete surgical transection, or a T8 laminectomy only. At 4wks after surgery, H-reflex recordings from the hindpaw plantar muscles of contused rats showed twice the amplitude of that in laminectomy controls or transected rats. To probe the role of 5-HT 2 R in this increased amplitude, dose response studies were done with the selective antagonists, mianserin or LY53857, and the 5-HT 2 R agonist, (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). The drugs were intrathecally infused into the lumbar cord while recording the H-reflex. Mianserin did not have any significant effects on the H-reflex after transection, consistent with the loss of distal serotonergic innervation. After contusion, both 5-HT 2 R antagonists reduced the H-reflex reflex amplitude with a significantly higher ID 50 compared to the uninjured controls. The 5-HT 2 R agonist, DOI, significantly increased reflex amplitude in contused but not control rats. Furthermore, while 5-HT immunoreactivity was similar, contused rats displayed increased 5-HT 2A R immunoreactivity in plantar muscle motoneurons compared to uninjured controls. We conclude that increased expression of 5-HT 2 R is likely to be involved in the enhanced H-reflex that develops after contusive SCI.

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“…It has been reported that 5-HT is the mediator of a slow excitatory postsynaptic potential (e.p.s.p.) in a population of motoneurones (Wang & Dun, 1990) and several studies have shown both excitatory and inhibitory effects of 5-HT on lamprey spinal cord neurones (Wallen et al, 1989) and on turtle or rat motoneurones (see Hounsgaard & Kiehn, 1989;Wang & Dun, 1990;Berger et al, 1992;Elliott & Wallis, 1992;Larkman & Kelly, 1992; Garratt et al, 1993;Ziskind-Conhaim et al, 1993).…”

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 andl-norepinephrine as mediators of altered excitability in neonatal rat motoneurons studied in vitro

Cited by 109 publications

References 41 publications

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

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

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