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Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1a , 5-HT1b and 5-HT3 receptors in the rat spinal cord

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Summary

Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1a , 5-HT1b and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4–T2) at the cervical level produced a marked decrease (∼−75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (∼20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (−12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.

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Abbreviations

CP 93129 :

3-(1,2,5,6-tetrahydropyrid-4-yl) pyrrolo [3,2-b]pyrid-5-one

5,7-DHT :

5,7-dihydroxytryptamine

DSP-4 :

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine

GTI :

serotonin-O-carboxymethylglycyl-iodotyrosinamide

HEPES :

4-(2-hydroxyethyl)-l-piperazine ethane sulfonic acid

5-HT :

5-hydroxytryptamine

i.c. :

intracisternally

NA :

noradrenaline

8-OH-DPAT :

8-hydroxy-2-(di-n-propylamino)tetralin

References

  • Adrien J, Lanfumey L, Gozlan H, Fattaccini CM, Hamon M (1989) Biochemical and electrophysiological evidence for an agonist action of CM 57493 at pre- and postsynaptic 5-hydroxytryptamine1A receptors in brain. J Pharmacol Exp Ther 248: 1222–1230

    PubMed  Google Scholar 

  • Alhaider AA, Lei SZ, Wilcox GL (1991) Spinal 5-HT3 receptor-mediated antinociception: possible release of GAB A. J Neurosci 11: 1881–1888

    PubMed  Google Scholar 

  • Bervoets K, Rivet JM, Millan MJ (1993) 5-HT1A receptors and the tail-flick response. IV. Spinally localized 5-HT1A receptors postsynaptic to serotoninergic neurones mediate spontaneous tail-flicks in the rat. J Pharmacol Exp Ther 264: 95–104

    PubMed  Google Scholar 

  • Besson JM, Chaouch A (1987) Descending serotoninergic systems. Pain Headache 9: 64–100

    PubMed  Google Scholar 

  • Blier P, Bouchard C (1993) Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea pig brain. Br J Pharmacol 108: 13–22

    PubMed  Google Scholar 

  • Boulenguez P, Segu L, Chauveau J, Morel A, Lanoir J, Delaage M (1992) Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl-[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites. J Neurochem 58: 951–959

    PubMed  Google Scholar 

  • Bruinvels AT, Landwehrmeyer B, Moskowitz MA, Hoyer D (1992) Evidence for the presence of 5-HT1B receptor messenger RNA in neurons of the rat trigeminal ganglia. Eur J Pharmacol Mol Pharmacol Sect 227: 357–359

    Google Scholar 

  • Bruinvels AT, Landwehrmeyer B, Gustafson EL, Durkin MM, Mengod G, Branchek TA, Hoyer D, Palacios JM (1994) Localization of 5-HT1B, 5-HT1Dα, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain. Neuropharmacology 33: 367–386

    PubMed  Google Scholar 

  • Carstens E, Klumpp D, Randic M, Zimmermann M (1981) Effects of iontophoretically applied 5-hydroxytryptamine on the excitability of single primary afferent C- and Afibers in the cat spinal cord. Brain Res 220: 151–158

    PubMed  Google Scholar 

  • Cesselin F, Bourgoin S, Artaud F, Hamon M (1984) Basic and regulatory mechanisms of in vitro release of met-enkephalin from the dorsal zone of the rat spinal cord. J Neurochem 43: 763–773

    PubMed  Google Scholar 

  • Cesselin F, Laporte AM, Miquel MC, Bourgoin S, Hamon M (1994) Serotonergic mechanisms of pain control. In: Gebhart GF, Hammond DL, Jensen TS (eds) Progress in pain research and management. Proceedings of the 7th World Congress on Pain, vol 2. IASP Press, Seattle, pp 669–695

    Google Scholar 

  • Crisp T, Stafinsky JL, Spanos LJ, Uram M, Perni V, Donepudi HB (1991) Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord. Gen Pharmacol 22: 247–251

    PubMed  Google Scholar 

  • Danzebrink RM, Gebhart GF (1991a) Evidence that spinal 5-HT1: 5-HT2 and 5-HT3 receptor subtypes modulate responses to noxious colorectal distension in the rat. Brain Res 538: 64–75

    PubMed  Google Scholar 

  • Danzebrink RM, Gebhart GF (1991b) Intrathecal coadministration of clonidine with serotonin agonists produces supra-additive visceral antinociception in the rat. Brain Res 555: 35–42

    PubMed  Google Scholar 

  • Daval G, Vergé D, Basbaum AI, Bourgoin S, Hamon M (1987) Autoradiographic evidence of serotonin1 binding sites on primary afferent fibres in the dorsal horn of the rat spinal cord. Neurosci Lett 83: 71–76

    PubMed  Google Scholar 

  • Delander GE, Hopkins CJ (1987) Interdependence of spinal adenosinergic, serotonergic and noradrenergic systems mediating antinociception. Neuropharmacology 26: 1791–1794

    PubMed  Google Scholar 

  • Doucet E, Pohl M, Fattaccini CM, Adrien J, El Mestikawy S, Hamon M (1994) In situ hybridization evidence for the synthesis of 5-HT1B receptor in serotoninergic neurons of anterior raphe nuclei in the rat brain. Synapse (in press)

  • Eide PK, Hole K, Berge OG, Broch OJ (1988) 5-HT depletion with 5,7-DHT, PCA and PCPA in mice: differential effects on the sensitivity to 5-MeODMT, 8-OH-DPAT and 5-HTP as measured by two nociceptive tests. Brain Res 440: 42–52

    PubMed  Google Scholar 

  • Eide PK, Joly NM, Hole K (1990) The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex. Brain Res 536: 195–200

    PubMed  Google Scholar 

  • Eide PK, Hole K, Broch OJ (1992) Supersensitivity to the antinociceptive effect of a 5-HT, receptor agonist after lesion of raphe-spinal serotonergic neurones. Pharmacol Toxicol 71: 62–64

    PubMed  Google Scholar 

  • Glaum SR, Proudfit HK, Anderson EG (1988) Reversal of the antinociceptive effects of intrathecally administered serotonin in the rat by a selective 5-HT3 receptor antagonist. Neurosci Lett 95: 313–317

    PubMed  Google Scholar 

  • Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M (1983) Identification of pesynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305: 140–142

    PubMed  Google Scholar 

  • Hamon M, Gallissot MC, Ménard F, Gozlan H, Bourgoin S, Vergé D (1989) 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol 164: 315–322

    PubMed  Google Scholar 

  • Hamon M, Collin E, Chantrel D, Daval G, Vergé D, Bourgoin S, Cesselin F (1990) Serotonin receptors and the modulation of pain. In: Besson JM (ed) Serotonin and pain. Elsevier, Amsterdam, pp 53–72

    Google Scholar 

  • Hamon MD, Collin E, Chantrel D, Vergé D, Bourgoin S (1991) The contribution of monoamines and their receptors to pain control. In: Basbaum AI, Besson JM (eds) Towards a new pharmacotherapy of pain. Dahlem workshop reports. Wiley, Chichester, pp 83–102

    Google Scholar 

  • Jaim-Etcheverry G, Zieher LM (1980) DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188: 513–523

    PubMed  Google Scholar 

  • Kidd EJ, Laporte AM, Langlois X, Fattaccini CM, Doyen C, Lombard MC, Gozlan H, Hamon M (1993) 5-HT3 receptors in the rat central nervous system are mainly located on nerve fibres and terminals. Brain Res 612: 289–298

    PubMed  Google Scholar 

  • Laporte AM, Lombard MC, Bourgoin S, Vergé D, Gozlan H, Hamon M (1991) Pre- and postsynaptic location of 5-HT3 receptors in the rat spinal cord. In: Langer SZ, Galzin AM, Costentin J (eds) Presynaptic receptors and neuronal transporters. Adv Biosci 82: 91–92

  • Laporte AM, Koscielniak T, Ponchant M, Vergé D, Hamon M, Gozlan H (1992) Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodozacopride and [3H]zacopride as radioligands. Synapse 10: 271–281

    PubMed  Google Scholar 

  • Laporte AM, Doyen C, Nevo IT, Chauveau J, Hauw JJ, Hamon M (1995) Differential distribution of serotonin 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT3 receptors in the human spinal cord. J Chem Neuroanat (in press)

  • Lombard MC, Besson JM (1989) Attempts to gauge the relative importance of pre- and post-synaptic effects of morphine on the transmission of noxious messages in the dorsal horn of the rat spinal cord. Pain 37: 335–345

    PubMed  Google Scholar 

  • Macor JE, Burkhart CA, Heym JH, Ives JL, Lebel LA, Newman ME, Nielsen JA, Ryan K, Schulz DW, Torgersen LK, Koe BK (1990) 3-(1,2,5,6-tetrahydropyrid-4-yl) pyrrolo [3,2-b] pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl) indole. J Med Chem 33: 2087–2093

    PubMed  Google Scholar 

  • Marlier L, Teilhac JR, Cerruti C, Privat A (1991) Autoradiographic mapping of 5-HT, 5-HT1a, 5-HT1B and 5-HT2 receptors in the rat spinal cord. Brain Res 550: 15–23

    PubMed  Google Scholar 

  • Matsumoto I, Combs MR, Jones DJ (1992) Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]5-hydroxytryptamine release. J Pharmacol Exp Ther 260: 614–626

    PubMed  Google Scholar 

  • Minor BG, Post C, Archer T (1985) Blockade of intrathecal 5-hydroxytryptamineinduced antinociception in rats by noradrenaline depletion. Neurosci Lett 54: 39–44

    PubMed  Google Scholar 

  • Miquel MC, Doucet E, Riad M, Adrien J, Vergé D, Hamon M (1992) Effect of the selective lesion of serotoninergic neurons on the regional distribution of 5-HT1A receptor mRNA in the rat brain. Mol Brain Res 14: 357–362

    PubMed  Google Scholar 

  • Mongeau R, De Montigny C, Blier P (1994) Activation of 5-HT3 receptors enhances the electrically evoked release of [3H] nor adrenaline in rat brain limbic structures. Eur J Pharmacol 256: 269–279

    PubMed  Google Scholar 

  • Nakagawa I, Omote K, Kitahata LM, Collins JG, Murata K (1990) Serotonergic mediation of spinal analgesia and its interaction with noradrenergic systems. Anesthesiology 73: 474–478

    PubMed  Google Scholar 

  • Olivéras JL, Besson JM (1992) Serotonin, stimulation-produced analgesia and spinal mechanisms of antinociception. In: Bradley PB, Handley SL, Cooper SJ, Barnes NM, Coote JH (eds) Serotonin, CNS receptors and brain function. Adv Biosci 85: 383–406

  • Pert A (1987) Cholinergic and catecholaminergic modulation of nociceptive reactions. Pain Headache 9: 1–63

    Google Scholar 

  • Pohl M, Benoliel JJ, Bourgoin S, Lombard MC, Mauborgne A, Taquet H, Carayon A, Besson JM, Cesselin F, Hamon M (1990) Regional distribution of calcitonin generelated peptide-, substance P-, cholecystokinin-, met5-enkephalin- and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin. J Neurochem 55: 1122–1130

    PubMed  Google Scholar 

  • Pompeiano M, Palacios JM, Mengod G (1992) Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci 12: 440–453

    PubMed  Google Scholar 

  • Post C, Minor BG, Davies M, Archer T (1986) Analgesia induced by 5-hydroxytryptamine receptor agonists is blocked or reversed by noradrenaline-depletion in rats. Brain Res 363: 18–27

    PubMed  Google Scholar 

  • Pubols LM, Bernau NA, Kane LA, Dawson SD, Burleigh AL, Polans AS (1992) Distribution of 5-HT1 binding sites in cat spinal cord. Neurosci Lett 142: 111–114

    PubMed  Google Scholar 

  • Reimann W, Schneider F (1993) The serotonin receptor agonist 5-methoxy-N, N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity. Gen Pharmacol 24: 449–453

    PubMed  Google Scholar 

  • Robertson B, Bevan S (1991) Properties of 5-hydroxytryptamine3 receptor-gated currents in adult rat dorsal root ganglion neurones. Br J Pharmacol 102: 272–276

    PubMed  Google Scholar 

  • Schmauss C, Hammond DL, Ochi JW, Yaksh TL (1983) Pharmacological antagonism of the antinociceptive effects of serotonin in the rat spinal cord. Eur J Pharmacol 90: 349–357

    PubMed  Google Scholar 

  • Snedecor GW, Cochran WG (1967) Statistical methods. Iowa State College Press, Ames

    Google Scholar 

  • Tecott LH, Maricq AV, Julius D (1993) Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci USA 90: 1430–1434

    PubMed  Google Scholar 

  • Thor KB, Nickolaus S, Helke CJ (1993) Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1c/2 binding sites in the rat spinal cord. Neuroscience 55: 235–252

    PubMed  Google Scholar 

  • Todorovic S, Anderson EG (1992) Serotonin preferentially hyperpolarizes capsaicinsensitive C type sensory neurons by activating 5-HT1A receptors. Brain Res 585: 212–218

    PubMed  Google Scholar 

  • Tuomisto J (1977) Nomifensine and its derivatives as possible tools for studying amine uptake. Eur J Pharmacol 42: 101–106

    PubMed  Google Scholar 

  • Vergé D, Daval G, Marcinkiewicz M, Patey A, El Mestikawy S, Gozlan H, Hamon M (1986) Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats. J Neurosci 6: 3474–3482

    PubMed  Google Scholar 

  • Williams GM, Smith DL, Smith DJ (1992) 5-HT3 receptors are not involved in the modulation of the K+-evoked release of [3H]5-HT from spinal cord synaptosomes of rat. Neuropharmacology 31: 725–733

    PubMed  Google Scholar 

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Author notes

  1. A. M. Laporte

    Present address: Faculté de Médecine Pitié-Salpêtrière, INSERM U288, Neurobiologie Cellulaire et Fonctionnellé, France

Authors and Affiliations

  1. Faculté de Médecine Pitié-Salpêtrière, INSERM U288, Neurobiologie Cellulaire et Fonctionnellé, France

    C. M. Fattaccini & M. Hamon

  2. INSERM U161, Physiopharmacologie du Système Nerveux, Paris

    M. C. Lombard

  3. IMMUNOTECH, Marseille, France

    J. Chauveau

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  1. A. M. Laporte
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  5. M. Hamon
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Laporte, A.M., Fattaccini, C.M., Lombard, M.C. et al. Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1a , 5-HT1b and 5-HT3 receptors in the rat spinal cord. J. Neural Transmission 100, 207–223 (1995). https://doi.org/10.1007/BF01276459

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  • DOI: https://doi.org/10.1007/BF01276459

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