Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1547–1555. doi: 10.1111/j.1476-5381.1991.tb09825.x

Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats.

K C Fone 1, A J Robinson 1, C A Marsden 1
PMCID: PMC1908369  PMID: 1832068

Abstract

1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1547

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnt J., Hyttel J. Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol. 1989 Feb 14;161(1):45–51. doi: 10.1016/0014-2999(89)90178-7. [DOI] [PubMed] [Google Scholar]
  2. Barbaccia M. L., Brunello N., Chuang D. M., Costa E. Serotonin-elicited amplification of adenylate cyclase activity in hippocampal membranes from adult rat. J Neurochem. 1983 Jun;40(6):1671–1679. doi: 10.1111/j.1471-4159.1983.tb08141.x. [DOI] [PubMed] [Google Scholar]
  3. Barbeau H., Bédard P. Similar motor effects of 5-HT and TRH in rats following chronic spinal transection and 5.7-dihydroxytryptamine injection. Neuropharmacology. 1981 May;20(5):477–481. doi: 10.1016/0028-3908(81)90181-7. [DOI] [PubMed] [Google Scholar]
  4. Barnes J. M., Barnes N. M., Costall B., Ironside J. W., Naylor R. J. Identification and characterisation of 5-hydroxytryptamine 3 recognition sites in human brain tissue. J Neurochem. 1989 Dec;53(6):1787–1793. doi: 10.1111/j.1471-4159.1989.tb09244.x. [DOI] [PubMed] [Google Scholar]
  5. Bedard P., Pycock C. J. "Wet-dog" shake behaviour in the rat: a possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology. 1977 Oct;16(10):663–670. doi: 10.1016/0028-3908(77)90117-4. [DOI] [PubMed] [Google Scholar]
  6. Bobker D. H., Williams J. T. Ion conductances affected by 5-HT receptor subtypes in mammalian neurons. Trends Neurosci. 1990 May;13(5):169–173. doi: 10.1016/0166-2236(90)90042-9. [DOI] [PubMed] [Google Scholar]
  7. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  8. Conn P. J., Sanders-Bush E. Agonist-induced phosphoinositide hydrolysis in choroid plexus. J Neurochem. 1986 Dec;47(6):1754–1760. doi: 10.1111/j.1471-4159.1986.tb13085.x. [DOI] [PubMed] [Google Scholar]
  9. Conn P. J., Sanders-Bush E. Selective 5HT-2 antagonists inhibit serotonin stimulated phosphatidylinositol metabolism in cerebral cortex. Neuropharmacology. 1984 Aug;23(8):993–996. doi: 10.1016/0028-3908(84)90017-0. [DOI] [PubMed] [Google Scholar]
  10. Connell L. A., Wallis D. I. 5-Hydroxytryptamine depolarizes neonatal rat motorneurones through a receptor unrelated to an identified binding site. Neuropharmacology. 1989 Jun;28(6):625–634. doi: 10.1016/0028-3908(89)90142-1. [DOI] [PubMed] [Google Scholar]
  11. Connell L. A., Wallis D. I. Responses to 5-hydroxytryptamine evoked in the hemisected spinal cord of the neonate rat. Br J Pharmacol. 1988 Aug;94(4):1101–1114. doi: 10.1111/j.1476-5381.1988.tb11628.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Connor H. E., Feniuk W., Humphrey P. P., Perren M. J. 5-Carboxamidotryptamine is a selective agonist at 5-hydroxytryptamine receptors mediating vasodilatation and tachycardia in anaesthetized cats. Br J Pharmacol. 1986 Feb;87(2):417–426. doi: 10.1111/j.1476-5381.1986.tb10832.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dumuis A., Sebben M., Bockaert J. BRL 24924: a potent agonist at a non-classical 5-HT receptor positively coupled with adenylate cyclase in colliculi neurons. Eur J Pharmacol. 1989 Mar 21;162(2):381–384. doi: 10.1016/0014-2999(89)90304-x. [DOI] [PubMed] [Google Scholar]
  14. Fone K. C., Bennett G. W., Marsden C. A. Involvement of catecholaminergic neurones and alpha-adrenoceptors in the wet-dog shake and forepaw licking behaviour produced by the intrathecal injection of an analogue of thyrotrophin-releasing hormone (CG 3509). Neuropharmacology. 1987 Aug;26(8):1147–1155. doi: 10.1016/0028-3908(87)90261-9. [DOI] [PubMed] [Google Scholar]
  15. Fone K. C., Johnson J. V., Bennett G. W., Marsden C. A. Involvement of 5-HT2 receptors in the behaviours produced by intrathecal administration of selected 5-HT agonists and the TRH analogue (CG 3509) to rats. Br J Pharmacol. 1989 Mar;96(3):599–608. doi: 10.1111/j.1476-5381.1989.tb11858.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Frazer A., Maayani S., Wolfe B. B. Subtypes of receptors for serotonin. Annu Rev Pharmacol Toxicol. 1990;30:307–348. doi: 10.1146/annurev.pa.30.040190.001515. [DOI] [PubMed] [Google Scholar]
  17. Fung S. J., Barnes C. D. Raphé-produced excitation of spinal cord motoneurons in the cat. Neurosci Lett. 1989 Aug 28;103(2):185–190. doi: 10.1016/0304-3940(89)90573-9. [DOI] [PubMed] [Google Scholar]
  18. Goodwin G. M., Green A. R. A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors. Br J Pharmacol. 1985 Mar;84(3):743–753. doi: 10.1111/j.1476-5381.1985.tb16157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hartig P. R. Molecular biology of 5-HT receptors. Trends Pharmacol Sci. 1989 Feb;10(2):64–69. doi: 10.1016/0165-6147(89)90080-1. [DOI] [PubMed] [Google Scholar]
  20. Hoyer D. Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res. 1988;8(1-4):59–81. doi: 10.3109/10799898809048978. [DOI] [PubMed] [Google Scholar]
  21. Hoyer D., Middlemiss D. N. Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain. Trends Pharmacol Sci. 1989 Apr;10(4):130–132. doi: 10.1016/0165-6147(89)90159-4. [DOI] [PubMed] [Google Scholar]
  22. Hylden J. L., Wilcox G. L. Intrathecal serotonin in mice: analgesia and inhibition of a spinal action of substance P. Life Sci. 1983 Aug 22;33(8):789–795. doi: 10.1016/0024-3205(83)90785-3. [DOI] [PubMed] [Google Scholar]
  23. Jackson H. C., Kitchen I. Behavioural profiles of putative 5-hydroxytryptamine receptor agonists and antagonists in developing rats. Neuropharmacology. 1989 Jun;28(6):635–642. doi: 10.1016/0028-3908(89)90143-3. [DOI] [PubMed] [Google Scholar]
  24. Jacobs B. L. An animal behavior model for studying central serotonergic synapses. Life Sci. 1976 Sep 15;19(6):777–785. doi: 10.1016/0024-3205(76)90303-9. [DOI] [PubMed] [Google Scholar]
  25. Jacobs B. L., Klemfuss H. Brain stem and spinal cord mediation of a serotonergic behavioral syndrome. Brain Res. 1975 Dec 19;100(2):450–457. doi: 10.1016/0006-8993(75)90500-4. [DOI] [PubMed] [Google Scholar]
  26. Johnson J. V., Fone K. C., Havler M. E., Tulloch I. F., Bennett G. W., Marsden C. A. A comparison of the motor behaviours produced by the intrathecal administration of thyrotrophin-releasing hormone and thyrotrophin-releasing hormone analogues in the conscious rat. Neuroscience. 1989;29(2):463–470. doi: 10.1016/0306-4522(89)90073-0. [DOI] [PubMed] [Google Scholar]
  27. Kennett G. A., Curzon G. Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol. 1988 May;94(1):137–147. doi: 10.1111/j.1476-5381.1988.tb11508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kilpatrick G. J., Jones B. J., Tyers M. B. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature. 1987 Dec 24;330(6150):746–748. doi: 10.1038/330746a0. [DOI] [PubMed] [Google Scholar]
  29. Larson A. A., Wilcox G. L. Synergistic behavioral effects of serotonin and tryptamine injected intrathecally in mice. Neuropharmacology. 1984 Dec;23(12A):1415–1418. doi: 10.1016/0028-3908(84)90082-0. [DOI] [PubMed] [Google Scholar]
  30. Leonhardt S., Titeler M. Serotonin 5-HT2 receptors: two states versus two subtypes. J Neurochem. 1989 Jul;53(1):316–318. doi: 10.1111/j.1471-4159.1989.tb07334.x. [DOI] [PubMed] [Google Scholar]
  31. Leysen J. E., Janssen P. F., Niemegeers C. J. Rapid desensitization and down-regulation of 5-HT2 receptors by DOM treatment. Eur J Pharmacol. 1989 Apr 12;163(1):145–149. doi: 10.1016/0014-2999(89)90409-3. [DOI] [PubMed] [Google Scholar]
  32. Lucki I., Nobler M. S., Frazer A. Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther. 1984 Jan;228(1):133–139. [PubMed] [Google Scholar]
  33. Lyon R. A., Davis K. H., Titeler M. 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors. Mol Pharmacol. 1987 Feb;31(2):194–199. [PubMed] [Google Scholar]
  34. McCall R. B., Aghajanian G. K. Serotonergic facilitation of facial motoneuron excitation. Brain Res. 1979 Jun 15;169(1):11–27. doi: 10.1016/0006-8993(79)90370-6. [DOI] [PubMed] [Google Scholar]
  35. McKenna D. J., Peroutka S. J. Differentiation of 5-hydroxytryptamine2 receptor subtypes using 125I-R-(-)2,5-dimethoxy-4-iodo-phenylisopropylamine and 3H-ketanserin. J Neurosci. 1989 Oct;9(10):3482–3490. doi: 10.1523/JNEUROSCI.09-10-03482.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Middlemiss D. N., Fozard J. R. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151–153. doi: 10.1016/0014-2999(83)90230-3. [DOI] [PubMed] [Google Scholar]
  37. Millan M. J., Bervoets K., Colpaert F. C. Apparent hyperalgesic action of the 5-HT1A agonist, 8-OH-DPAT, in the rat reflects induction of spontaneous tail-flicks. Neurosci Lett. 1989 Dec 15;107(1-3):227–232. doi: 10.1016/0304-3940(89)90822-7. [DOI] [PubMed] [Google Scholar]
  38. Peroutka S. J. 5-Hydroxytryptamine receptor subtypes. Annu Rev Neurosci. 1988;11:45–60. doi: 10.1146/annurev.ne.11.030188.000401. [DOI] [PubMed] [Google Scholar]
  39. Rasmussen K., Aghajanian G. K. Serotonin excitation of facial motoneurons: receptor subtype characterization. Synapse. 1990;5(4):324–332. doi: 10.1002/syn.890050409. [DOI] [PubMed] [Google Scholar]
  40. Roberts M. H., Davies M., Girdlestone D., Foster G. A. Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation. Br J Pharmacol. 1988 Oct;95(2):437–448. doi: 10.1111/j.1476-5381.1988.tb11664.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Toda N., Okamura T. Comparison of the response to 5-carboxamidotryptamine and serotonin in isolated human, monkey and dog coronary arteries. J Pharmacol Exp Ther. 1990 May;253(2):676–682. [PubMed] [Google Scholar]
  42. Tricklebank M. D., Forler C., Fozard J. R. The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol. 1984 Nov 13;106(2):271–282. doi: 10.1016/0014-2999(84)90714-3. [DOI] [PubMed] [Google Scholar]
  43. Ulfhake B., Arvidsson U., Cullheim S., Hökfelt T., Brodin E., Verhofstad A., Visser T. An ultrastructural study of 5-hydroxytryptamine-, thyrotropin-releasing hormone- and substance P-immunoreactive axonal boutons in the motor nucleus of spinal cord segments L7-S1 in the adult cat. Neuroscience. 1987 Dec;23(3):917–929. doi: 10.1016/0306-4522(87)90168-0. [DOI] [PubMed] [Google Scholar]
  44. Waeber C., Hoyer D., Palacios J. M. 5-hydroxytryptamine3 receptors in the human brain: autoradiographic visualization using [3H]ICS 205-930. Neuroscience. 1989;31(2):393–400. doi: 10.1016/0306-4522(89)90382-5. [DOI] [PubMed] [Google Scholar]
  45. White S. R., Neuman R. S. Facilitation of spinal motoneurone excitability by 5-hydroxytryptamine and noradrenaline. Brain Res. 1980 Apr 21;188(1):119–127. doi: 10.1016/0006-8993(80)90561-2. [DOI] [PubMed] [Google Scholar]
  46. Yaksh T. L., Rudy T. A. Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 1976 Dec;17(6):1031–1036. doi: 10.1016/0031-9384(76)90029-9. [DOI] [PubMed] [Google Scholar]
  47. Yap C. Y., Taylor D. A. Involvement of 5-HT2 receptors in the wet-dog shake behaviour induced by 5-hydroxytryptophan in the rat. Neuropharmacology. 1983 Jul;22(7):801–804. doi: 10.1016/0028-3908(83)90123-5. [DOI] [PubMed] [Google Scholar]
  48. Yocca F. D., Wright R. N., Margraf R. R., Eison A. S. 8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shake response in rats. Pharmacol Biochem Behav. 1990 Jan;35(1):251–254. doi: 10.1016/0091-3057(90)90234-9. [DOI] [PubMed] [Google Scholar]
  49. Yusof A. P., Coote J. H. Excitatory and inhibitory actions of intrathecally administered 5-hydroxytryptamine on sympathetic nerve activity in the rat. J Auton Nerv Syst. 1988 Apr;22(3):229–236. doi: 10.1016/0165-1838(88)90111-7. [DOI] [PubMed] [Google Scholar]
  50. el-Yassir N., Fleetwood-Walker S. M., Mitchell R. Heterogeneous effects of serotonin in the dorsal horn of rat: the involvement of 5-HT1 receptor subtypes. Brain Res. 1988 Jul 19;456(1):147–158. doi: 10.1016/0006-8993(88)90356-3. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES