Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT 1B and 5-HT 1F receptors

Journal of Neurophysiology

Volumn 106, Issue 2, 2011, Pages 925-943

  Murray, Katherine C ^a   Stephens, Marilee J ^a   Rank, Michelle ^a   D'Amico, Jessica ^a   Gorassini, Monica A ^a   Bennett, David J ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Motoneurons; Muscle spasms; Serotonin; Spasticity; Synaptic input; Triptans

Indexed keywords

1 [5 (2 THIENYLMETHOXY) 3 INDOLYL] 2 PROPANAMINE; 2,3,6,7 TETRAHYDRO 1' METHYL 5 [[2' METHYL 4' (5 METHYL 1,2,4 OXADIAZOL 3 YL) 4 BIPHENYLYL]CARBONYL]SPIRO[FURO[2,3 F]INDOLE 3,4' PIPERIDINE]; EMD 386088; METHYLERGOMETRINE; N (3 DIMETHYLAMINO 2,3,4,9 TETRAHYDRO 1H CARBAZOL 6 YL) 4 FLUOROBENZAMIDE; N [4 METHOXY 3 (4 METHYL 1 PIPERAZINYL)PHENYL] 2' METHYL 4' (5 METHYL 1,2,4 OXADIAZOL 3 YL)[1,1' BIPHENYL] 4 CARBOXAMIDE; SB 216641; SEROTONIN 1B ANTAGONIST; SEROTONIN 1B RECEPTOR; SEROTONIN 1F RECEPTOR; SEROTONIN AGONIST; SEROTONIN ANTAGONIST; UNCLASSIFIED DRUG; ZOLMITRIPTAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG MECHANISM; DRUG RECEPTOR BINDING; EXCITATORY POSTSYNAPTIC POTENTIAL; IN VITRO STUDY; INHIBITORY POSTSYNAPTIC POTENTIAL; MEMBRANE STEADY POTENTIAL; MUSCLE SPASM; NONHUMAN; POLYSYNAPTIC REFLEX; POSTSYNAPTIC POTENTIAL; PRIORITY JOURNAL; RAT; SPINAL CORD INJURY;

ANIMALS; ELECTRIC STIMULATION; EXCITATORY POSTSYNAPTIC POTENTIALS; FEMALE; NEURAL INHIBITION; RATS; RECEPTOR, SEROTONIN, 5-HT1B; RECEPTORS, SEROTONIN; SACRUM; SEROTONIN 5-HT1 RECEPTOR AGONISTS; SPASM; SPINAL CORD INJURIES;

EID: 80051529261     PISSN: 00223077     EISSN: 15221598     Source Type: Journal    
DOI: 10.1152/jn.01011.2010     Document Type: Article

References (87)

1. Adham N, Gerald C, Schechter L, Vaysse P, Weinshank R, Branchek T. [3H]5-hydroxytryptamine labels the agonist high affinity state of the cloned rat 5-HT4 receptor. Eur J Pharmacol 304: 231-235, 1996.
2. Ashby P, McCrea DA. Neurophysiology of spinal spasticity. In: Handbook of the Spinal Cord, edited by Davidoff RA. New York: Dekker, 1987, p. 119-143.
3. Baker LL, Chandler SH. Characterization of postsynaptic potentials evoked by sural nerve stimulation in hindlimb motoneurons from acute and chronic spinal cats. Brain Res 420: 340-350, 1987.
4. Baxter GS. Novel discriminatory ligands for 5-HT2B receptors. Behav Brain Res 73: 149-152, 1996.
5. Bennett DJ, Gorassini M, Fouad K, Sanelli L, Han Y, Cheng J. Spasticity in rats with sacral spinal cord injury. J Neurotrauma 16: 69-84, 1999.
6. Bennett DJ, Hultborn H, Fedirchuk B, Gorassini M. Synaptic activation of plateaus in hindlimb motoneurons of decerebrate cats. J Neurophysiol 80: 2023-2037, 1998.
7. Bennett DJ, Li Y, Harvey PJ, Gorassini M. Evidence for plateau potentials in tail motoneurons of awake chronic spinal rats with spasticity. J Neurophysiol 86: 1972-1982, 2001.
8. Bennett DJ, Sanelli L, Cooke C, Harvey PJ, Gorassini MA. Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury. J Neurophysiol 91: 2247-2258, 2004.
9. Berg RW, Alaburda A, Hounsgaard J. Balanced inhibition and excitation drive spike activity in spinal half-centers. Science 315: 390-393, 2007.
10. Berg RW, Hounsgaard J. Signaling in large-scale neural networks. Cogn Process 10, Suppl 1: S9-S15, 2009.
11. Boess FG, Martin IL. Molecular biology of 5-HT receptors. Neuropharmacology 33: 275-317, 1994.
12. Boess FG, Monsma FJ Jr, Carolo C, Meyer V, Rudler A, Zwingelstein C, Sleight AJ. Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells. Neuropharmacology 36: 713-720, 1997.
13. Boulenguez P, Liabeuf S, Bos R, Bras H, Jean-Xavier C, Brocard C, Stil A, Darbon P, Cattaert D, Delpire E, Marsala M, Vinay L. Downregulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med 16: 302-307, 2010.
14. Button DC, Kalmar JM, Gardiner K, Marqueste T, Zhong H, Roy RR, Edgerton VR, Gardiner PF. Does elimination of afferent input modify the changes in rat motoneurone properties that occur following chronic spinal cord transection? J Physiol 586: 529-544, 2008.
15. Clarke RW, Eves S, Harris J, Peachey JE, Stuart E. Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems. Neuroscience 112: 555-571, 2002.
16. Clarke RW, Harris J, Houghton AK. Spinal 5-HT-receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit. Br J Pharmacol 119: 1167-1176, 1996.
17. Dario A, Tomei G. A benefit-risk assessment of baclofen in severe spinal spasticity. Drug Saf 27: 799-818, 2004.
18. Di Pasquale E, Lindsay A, Feldman J, Monteau R, Hilaire G. Serotonergic inhibition of phrenic motoneuron activity: an in vitro study in neonatal rat. Neurosci Lett 230: 29-32, 1997.
19. Dietz V, Sinkjaer T. Spastic movement disorder: impaired reflex function and altered muscle mechanics. Lancet Neurol 6: 725-733, 2007.
20. Dougherty KJ, Bannatyne BA, Jankowska E, Krutki P, Maxwell DJ. Membrane receptors involved in modulation of responses of spinal dorsal horn interneurons evoked by feline group II muscle afferents. J Neurosci 25: 584-593, 2005.
21. Egan C, Grinde E, Dupre A, Roth BL, Hake M, Teitler M, Herrick-Davis K. Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT2A and 5-HT2C receptors. Synapse 35: 144-150, 2000.
22. 1B binding sites. Naunyn Schmiedebergs Arch Pharmacol 332: 1-7, 1986.
23. Gilmore J, Fedirchuk B. The excitability of lumbar motoneurones in the neonatal rat is increased by a hyperpolarization of their voltage threshold for activation by descending serotonergic fibres. J Physiol 558: 213-224, 2004.
24. Glennon RA, Ismaiel AE, McCarthy BG, Peroutka SJ. Binding of arylpiperazines to 5-HT3 serotonin receptors: results of a structure-affinity study. Eur J Pharmacol 168: 387-392, 1989.
25. Gorassini M, Yang JF, Siu M, Bennett DJ. Intrinsic activation of human motoneurons: possible contribution to motor unit excitation. J Neurophysiol 87: 1850-1858, 2002.
26. Gorassini MA, Knash ME, Harvey PJ, Bennett DJ, Yang JF. Role of motoneurons in the generation of muscle spasms after spinal cord injury. Brain 127: 2247-2258, 2004.
27. Gorassini MA, Norton JA, Nevett-Duchcherer J, Roy FD, Yang JF. Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury. J Neurophysiol 101: 969-979, 2009.
28. Hammar I, Jankowska E. Modulatory effects of alpha1-,alpha2-, and betareceptor agonists on feline spinal interneurons with monosynaptic input from group I muscle afferents. J Neurosci 23: 332-338, 2003.
29. Hammar I, Stecina K, Jankowska E. Differential modulation by monoamine membrane receptor agonists of reticulospinal input to lamina VIII feline spinal commissural interneurons. Eur J Neurosci 26: 1205-1212, 2007.
30. Harris RL, Bobet J, Sanelli L, Bennett DJ. Tail muscles become slow but fatigable in chronic sacral spinal rats with spasticity. J Neurophysiol 95: 1124-1133, 2006.
31. Harvey PJ, Li X, Li Y, Bennett DJ. 5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury. J Neurophysiol 96: 1158-1170, 2006.
32. Harvey PJ, Li X, Li Y, Bennett DJ. Endogenous monoamine receptor activation is essential for enabling persistent sodium currents and repetitive firing in rat spinal motoneurons. J Neurophysiol 96: 1171-1186, 2006.
33. Harvey PJ, Li Y, Li X, Bennett DJ. Persistent sodium currents and repetitive firing in motoneurons of the sacrocaudal spinal cord of adult rats. J Neurophysiol 96: 1141-1157, 2006.
34. Heckman CJ. Alterations in synaptic input to motoneurons during partial spinal cord injury. Med Sci Sports Exerc 26: 1480-1490, 1994.
35. Heckman CJ, Gorassini MA, Bennett DJ. Persistent inward currents in motoneuron dendrites: implications for motor output. Muscle Nerve 31: 135-156, 2005.
36. Holstege JC, Bongers CM. A glycinergic projection from the ventromedial lower brainstem to spinal motoneurons. An ultrastructural double labeling study in rat. Brain Res 566: 308-315, 1991.
37. Hoyer D, Engel G, Kalkman HO. Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol 118: 13-23, 1985.
38. Hultborn H, Brownstone RB, Toth TI, Gossard JP. Key mechanisms for setting the input-output gain across the motoneuron pool. Prog Brain Res 143: 77-95, 2004.
39. Ismaiel AM, Titeler M, Miller KJ, Smith TS, Glennon RA. 5-HT1 and 5-HT2 binding profiles of the serotonergic agents alpha-methylserotonin and 2-methylserotonin. J Med Chem 33: 755-758, 1990.
40. Jankowska E. Interneuronal relay in spinal pathways from proprioceptors. Prog Neurobiol 38: 335-378, 1992.
41. Jankowska E. Spinal interneuronal networks in the cat: elementary components. Brain Res Rev 57: 46-55, 2008.
42. Jankowska E, Hammar I. Spinal interneurones; how can studies in animals contribute to the understanding of spinal interneuronal systems in man? Brain Res Brain Res Rev 40: 19-28, 2002.
43. Jankowska E, Hammar I, Chojnicka B, Heden CH. Effects of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents. Eur J Neurosci 12: 701-714, 2000.
44. Jankowska E, Lackberg ZS, Dyrehag LE. Effects of monoamines on transmission from group II muscle afferents in sacral segments in the cat. Eur J Neurosci 6: 1058-1061, 1994.
45. Jankowska E, Riddell JS, Skoog B, Noga BR. Gating of transmission to motoneurones by stimuli applied in the locus coeruleus and raphe nuclei of the cat. J Physiol 461: 705-722, 1993.
46. Jordan LM, Liu J, Hedlund PB, Akay T, Pearson KG. Descending command systems for the initiation of locomotion in mammals. Brain Res Rev 57: 183-191, 2008.
47. Kennett GA, Ainsworth K, Trail B, Blackburn TP. BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in rats. Neuropharmacology 36: 233-239, 1997.
48. Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M. Pharmacological characterisation of the agonist radioligand binding site of 5-HT2A, 5-HT2B and 5-HT2C receptors. Naunyn Schmiedebergs Arch Pharmacol 370: 114-123, 2004.
49. Kuhn RA, Macht MB. Some manifestations of reflex activity in spinal man with particular reference to the occurrence of extensor spasm. Bull Johns Hopkins Hosp 84: 43-75, 1948.
50. Leopoldo M, Lacivita E, Contino M, Colabufo NA, Berardi F, Perrone R. Structure-activity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1- yl)-4-aryl-1-piperazinehexanamides, a class of 5-HT7 receptor agents. J Med Chem 50: 4214-4221, 2007.
51. Li X, Bennett DJ. Apamin-sensitive calcium-activated potassium currents (SK) are activated by persistent calcium currents in rat motoneurons. J Neurophysiol 97: 3314-3330, 2007.
52. Li X, Murray K, Harvey PJ, Ballou EW, Bennett DJ. Serotonin facilitates a persistent calcium current in motoneurons of rats with and without chronic spinal cord injury. J Neurophysiol 97: 1236-1246, 2007.
53. Li Y, Bennett DJ. Persistent sodium and calcium currents cause plateau potentials in motoneurons of chronic spinal rats. J Neurophysiol 90: 857-869, 2003.
54. Li Y, Gorassini MA, Bennett DJ. Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats. J Neurophysiol 91: 767-783, 2004.
55. Li Y, Harvey PJ, Li X, Bennett DJ. Spastic long-lasting reflexes in the chronic spinal rat, studied in vitro. J Neurophysiol 91: 2236-2246, 2004.
56. Li Y, Li X, Harvey PJ, Bennett DJ. Effects of baclofen on spinal reflexes and persistent inward currents in motoneurons of chronic spinal rats with spasticity. J Neurophysiol 92: 2694-2703, 2004.
57. Lundberg A. Inhibitory control from the brainstem of transmission from primary afferents to motoneurons, primary afferent terminals and ascending pathways. In: Brainstem Control of Spinal Mechanisms, edited by Sjolund B and Bjorklund A. New York: Elsevier, 1982, p. 179-224.
58. Manuel NA, Wallis DI, Crick H. Ketanserin-sensitive depressant actions of 5-HT receptor agonists in the neonatal rat spinal cord. Br J Pharmacol 116: 2647-2654, 1995.
59. 1B/1D receptor partial agonist, 311C90 (zolmitriptan). Br J Pharmacol 121: 157-164, 1997.
60. Mattsson C, Sonesson C, Sandahl A, Greiner HE, Gassen M, Plaschke J, Leibrock J, Bottcher H. 2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1Hindoles as novel 5-HT6 receptor agonists. Bioorg Med Chem Lett 15: 4230-4234, 2005.
61. Maynard FM, Karunas RS, Waring WP 3rd. Epidemiology of spasticity following traumatic spinal cord injury. Arch Phys Med Rehabil 71: 566-569, 1990.
62. Mestre C, Pelissier T, Fialip J, Wilcox G, Eschalier A. A method to perform direct transcutaneous intrathecal injection in rats. J Pharmacol Toxicol Methods 32: 197-200, 1994.
63. Milburn CM, Peroutka SJ. Characterization of [3H]quipazine binding to 5-hydroxytryptamine3 receptors in rat brain membranes. J Neurochem 52: 1787-1792, 1989.
64. Millan MJ. Descending control of pain. Prog Neurobiol 66: 355-474, 2002.
65. Monsma FJ Jr, Shen Y, Ward RP, Hamblin MW, Sibley DR. Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 43: 320-327, 1993.
66. Murray K, Nakae A, Stephens MJ, Rank M, D'Amico J, Harvey P, Li X, Harris L, Ballou EW, Anelli R, Heckman CJ, Mashimo T, Vavrek R, Sanelli L, Gorassini MA, Bennett DJ, Fouad K. Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors. Nat Med 16: 694-700, 2010.
67. Murray K, Stephens MJ, Ballou EW, Anelli R, Heckman CJ, Bennett DJ. Motoneuron excitability and muscle spasms are regulated by 5-HT2B and 5-HT2C receptor activity. J Neurophysiol 105: 731-278, 2011.
68. Nielsen JB, Crone C, Hultborn H. The spinal pathophysiology of spasticity-from a basic science point of view. Acta Physiol (Oxf) 189: 171-180, 2007.
69. Norton JA, Bennett DJ, Knash ME, Murray KC, Gorassini MA. Changes in sensory-evoked synaptic activation of motoneurons after spinal cord injury in man. Brain 131: 1478-1491, 2008.
70. Noth J. Trends in the pathophysiology and pharmacotherapy of spasticity. J Neurol 238: 131-139, 1991.
71. Obata H, Saito S, Sakurazawa S, Sasaki M, Usui T, Goto F. Antiallodynic effects of intrathecally administered 5-HT2C receptor agonists in rats with nerve injury. Pain 108: 163-169, 2004.
72. + current in the adult turtle. J Physiol 548: 485-492, 2003.
73. Perrier JF, Delgado-Lezama R. Synaptic release of serotonin induced by stimulation of the raphe nucleus promotes plateau potentials in spinal motoneurons of the adult turtle. J Neurosci 25: 7993-7999, 2005.
74. Perrier JF, Hounsgaard J. 5-HT2 receptors promote plateau potentials in turtle spinal motoneurons by facilitating an L-type calcium current. J Neurophysiol 89: 954-959, 2003.
75. Phebus LA, Johnson KW, Zgombick JM, Gilbert PJ, Van Belle K, Mancuso V, Nelson DL, Calligaro DO, Kiefer AD Jr, Branchek TA, Flaugh ME. Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine. Life Sci 61: 2117-2126, 1997.
76. Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ. Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells. Br J Pharmacol 128: 13-20, 1999.
77. 1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol 356: 312-320, 1997.
78. Rekling JC, Funk GD, Bayliss DA, Dong XW, Feldman JL. Synaptic control of motoneuronal excitability. Physiol Rev 80: 767-852, 2000.
79. Schmidt BJ, Jordan LM. The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord. Brain Res Bull 53: 689-710, 2000.
80. Seifert R, Wenzel-Seifert K. Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn Schmiedebergs Arch Pharmacol 366: 381-416, 2002.
81. 1B receptor antagonist with negative intrinsic activity. Br J Pharmacol 125: 202-208, 1998.
82. Singer JH, Bellingham MC, Berger AJ. Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons by serotonin. J Neurophysiol 76: 799-807, 1996.
83. Steg G. Efferent muscle innervation and rigidity. Acta Physiol Scand Suppl 225: 1-53, 1964.
84. Taylor J, Munson J, Vierck C Jr. Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats. Eur J Neurosci 11: 363-368, 1999.
85. Udina E, D'Amico J, Bergquist AJ, Gorassini MA. Amphetamine increases persistent inward currents in human motoneurons estimated from paired motor-unit activity. J Neurophysiol 103: 1295-1303, 2010.
86. Wainscott DB, Cohen ML, Schenck KW, Audia JE, Nissen JS, Baez M, Kursar JD, Lucaites VL, Nelson DL. Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor. Mol Pharmacol 43: 419-426, 1993.
87. Yoshimura M, Furue H. Mechanisms for the anti-nociceptive actions of the descending noradrenergic and serotonergic systems in the spinal cord. J Pharmacol Sci 101: 107-117, 2006.