Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-16T15:05:36.211Z Has data issue: false hasContentIssue false
  • English
  • Français

Action of 5-Hydroxytryptamine, Substance P, Thyrotropin-Releasing Hormone and Clonidine on Motoneurone Excitability

Published online by Cambridge University Press:  05 January 2016

Paul J. Bédard ,
L.E. Tremblay ,
H. Barbeau ,
M. Filion ,
R. Maheux ,
C.L. Richards  and
T. DiPaolo
Paul J. Bédard*
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
L.E. Tremblay
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
H. Barbeau
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
M. Filion
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
R. Maheux
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
C.L. Richards
Affiliation:
Laboratoire de Neurobiologie, Faculté de Médicine, Université Laval, Québec
T. DiPaolo
Affiliation:
Département d'endocrinologie moléculaire, Centre Hospitalier de l'Université Laval, Québec
*
Laboratoire de Neurobiologie, Hôpital de l'Enfant-Jésus, 1401, 18e Rue, Québec, Québec, Canada GIJ 1Z4
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (LP.), 5-HT (intrathecally) TRH (LP. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 506 - 509
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Davidoff, RA.Antipasticity drugs: Mechanisms of action. Ann Neurol 1985; 17: 107–116.CrossRefGoogle ScholarPubMed
2.Dahlström, A, Fuxe, K.Evidence for the existence of monoamine neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta Physiol Scand 1965; Suppl. 247, 64: 1–36.Google Scholar
3.Johansson, O, Hökfelt, T, Pernow, B, et al. Immunohistochemical support for three putative transmitters in a neuron: coexistence of 5-HT, substance ? and TRH-like immunoreactivity in medullary neurons projecting to the spinal cord. Neurosci 1981; 6: 1857–1881.CrossRefGoogle Scholar
4.Steinbusch, HWM.Distribution of serotonin-immunoreactivity in the central nervous system of the rat. Cell Bodies and Terminals. Neuroscience 1981; 6: 557–618.CrossRefGoogle ScholarPubMed
5.Björklund, A, Wiklund, L, Descarries, L.Regeneration and plasticity of central serotoninergic neurons: a review. J Physiol Paris 77: 247–255.Google Scholar
6.Hökfelt, T, Ljungdahl, S, Steinbusch, H, et al. Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine containing neurons in the rat central nervous system. Neuroscience 1978; 3: 517–538.CrossRefGoogle ScholarPubMed
7.Hökfelt, T, Lundberg, J, Schultzberg, M, et al. Co-existence of peptides and putative transmitters in neurons. In neural peptides and neuronal communication. Costa, E, Trabucchi, M, eds. Raven Press, New York, 1980: 1–23.Google Scholar
8.Pelletier, G, Steinbush, HWM, Verhofstad, AAJ. Immunoreactive substance P and serotonin present in the same dense-core vesicles. Nature (Lond.) 1981; 293: 71–72.Google Scholar
9.Barbeau, H, Bédard, P.Similar motor effects of 5-HT and TRH in rats following chronic spinal transection and 5–7 Dihydroxy-tryptamine injection. Neuropharmacol 1981b; 20: 477–481.CrossRefGoogle Scholar
10.Tremblay, LE, Bédard, PJ, Maheux, R, et al. Denervation supersensitivity to 5-hydroxytryptamine in the rat spinal cord is not due to absence of 5-hydroxytrypamine. Brain Res 1985; 330: 174–177.CrossRefGoogle ScholarPubMed
11.Tremblay, LE, Bédard, PJ. Effects of clonidine on motoneuron excitability in spinalized rats. Neuropharmacol 1986; 25: 41–46.CrossRefGoogle ScholarPubMed
12.Bédard, PJ, Barbeau, H, Barbeau, G, et al. Progressive increase of motor activity induced by 5-HTP in the rat below a complete section of the spinal cord. Brain Res 1979; 169: 393–397.CrossRefGoogle Scholar
13.Barbeau, H, Filion, M, Bédard, PJ.Effects of agonists and antagonists of serotonin on spontaneous hindlimb EMG activity in chronic spinal rats. Neuropharmacol 1981; 20: 611–616.CrossRefGoogle ScholarPubMed
14.Barbeau, H, Bédard, PJ.Denervation supersensitivity to 5-hydroxy-tryptophan (5-HTP) in rats following spinal transection and 5–7 Dihydroxytryptamine injection. Neuropharmacol 1981; 20: 611–616.CrossRefGoogle ScholarPubMed
15.White, SR, Neuman, RS.Facilitation of spinal motoneurone excitability by 5-hydroxyptamineand noradrenaline. Brain Res 1980; 188: 119–127.CrossRefGoogle ScholarPubMed
16.White, SR, Neuman, RS.Pharmacological antagonism of facilitatory but not inhibitory effect of serotonin and norepinephrine on excitability of spinal motoneurons. Neuropharmacol 1983; 22: 489–494.CrossRefGoogle Scholar
17.Komissarov, IV, Abramets, II.Effect of monoamines on motoneurons of the isolated rat spinal cord translate VDC 612:83:612.822 1981 from Neirofiziologiya 1981; 12: 391–396.Google Scholar
18.Agnati, LF, Fuxe, K, Benfenati, F, et al. On the functional role of coexistence of 5-HT and substance P in bulbospinal 5-HT. Substance P reduces affinity and increases density of 3H-5HT binding sites. Acta Physiol Scand 1983; 117: 299–301.CrossRefGoogle Scholar
19.Sharif, NA, Burt, DR, Towle, AC, et al. Codepletion of serotonin and TRH induces apparent supersensitivity of spinal TRH receptors. Europ J Pharmacol 1983; 95: 301–304.CrossRefGoogle ScholarPubMed
20.Barbeau, H, Richards, CL, Bédard, PJ. Action of cyproheptadine in spastic paraplegic patients. J Neurol Neurosurg Psychiat 1982; 45: 923–926.CrossRefGoogle Scholar
21.Wainberg, M, Barbeau, H, Gauther, S.Quantitative assessment of the effect of cyproheptadine on spastic paretic gait: a preliminary study. J Neurol 1986; 233: 311–314.CrossRefGoogle ScholarPubMed
22.Konischi, S, Otsuka, M.Excitatory action of hypothalamic substance P on spinal motoneurons of newborn rats. Nature 1974; 252: 734–735.CrossRefGoogle Scholar
23.Henry, JL, Krnjevic, K, Morris, ME.Substance P and spinal neurones. Can J Physiol Pharmacol 1975; 53: 423–432.CrossRefGoogle ScholarPubMed
24.Nicoll, RA.The action of thyrotropin releasing hormone, substance P, and related peptides on frog spinal motoneurons. J Pharmacol Exp Ther 1978; 207: 817–824.Google ScholarPubMed
25.Tremblay, LE, Maheux, R, Bédard, PJ.Substance P in the lumbar spinal cord of the rat affects the motor response to 5-HTP and TRH. Neuropharmacol 1986; 25: 419–424.CrossRefGoogle ScholarPubMed
26.Sharif, NA, Burt, DR.Micromolar substance P reduces spinal receptor binding for thyrotropin-releasing hormone. Possible relevance to neuropeptide coexistence? Neuroscience letters 1983; 43: 245–251.CrossRefGoogle ScholarPubMed
27.Prasad, C, Edwards, RM.Thyrotropin-releasing hormone (TRH): apparent receptor binding in rat spinal cord. Brain Res 1984; 311: 1.CrossRefGoogle ScholarPubMed
28.Sharif, NA, Burt, DR.Limbic, hypothalamic, cortical and spinal regions are enriched in receptors for thyrotropin-releasing hormone: evidence from [3H] ultrafilm auto-radiography and correlation with central effects of the tripeptides in rat brain. Neurosc Lett 1985; 60: 337–342.CrossRefGoogle Scholar
29.Engel, WK, Siddique, T, Nicoloff, JT.Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone. The Lancet 1983; 8341: 73–75.CrossRefGoogle Scholar
30.Forssberg, H, Grillner, S.The locomotion of the acute spinal cat injected with clonidine i.v. Brain Res 1973; 50: 184–186.CrossRefGoogle ScholarPubMed
31.Barbeau, H, Rossignol, S.Modulation of the locomotor pattern by noradrenergic, serotonergic and dopaminergic agonists in the adult chronic spinal cat. Abstracts #47.3 Society for Neuroscience Minneapolis, 1982, p. 163.Google Scholar
32.Naftchi, NE.Functional restoration of the traumatically injured spinal cord in cats by clonidine. Science 1982: 217: 1042–1044.CrossRefGoogle ScholarPubMed
33.Nance, PW, Shears, AH, Nance, DM.Clonidine in spinal cord injury. Can Med Assoc J 1985; 133: 41–42.Google ScholarPubMed
34.Galeano, C, Jubelin, B, Carmel, M, et al. Urodynamic action of clonidine in the chronic spinal cat. Neurol Urodynam 1986; 5: 475–492.CrossRefGoogle Scholar