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Decrease in Gastric Sensitivity to Distension by 5-HT1A Receptor Agonists in Rats

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Abstract

Using an in vivo model for evaluation of gastricsensitivity in awake rats, we aimed to determine whether5-hydroxytryptamine 1A (5-HT1A) agonistsmodify pain threshold and gastric compliancespecifically through 5-HT1A receptors. Isobaricgastric distensions were performed with a barostat usingsteps of 5 mm Hg in male rats equipped with a gastricballoon and electrodes implanted in the neck muscles.Gastric distension at 15 or 20 mm Hg induced a typicalposture associated with contractions of the neckmuscles. Rats received drugs 30 min before gastricdistension. The 5-HT receptor agonist8-hydroxy-2-(di-n-propylamino)tetra1A lin (8-OH-DPAT),administered intraperitoneally (0.5 mg/kg) increasedgastric pain threshold and gastric tone. These effectswere reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricularadministration of the 5-HT1A antagonist WAY100635. Flesinoxan (4 mg/kg, intraperitoneally), another5-HT1A agonist reproduced the effects of8-OH-DPAT on pain threshold and gastric tone and the alpha-receptorantagonist yohimbine did not modify the action of8-OH-DPAT. Our results indicate that activation of5-HT1A receptors at the level of the centralnervous system increases gastric tone and decreases gastric sensitivityto distension.

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REFERENCES

  1. Lemann M, Dederding JP, Flourie B, Franchisseur C, Rambaud JC, Jian R: Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Dig Dis Sci 36:1249 - 1254, 1991

    PubMed  Google Scholar 

  2. Coffin B, Azpiroz F, Guarner F, Malagelada JR: Selective gastric hypersensitivity and reflex hyporeactivity in functional dyspepsia. Gastroenterology 107:1345 - 1351, 1994

    PubMed  Google Scholar 

  3. Bueno L, Fioramonti J, Delvaux M, Frexinos J: Mediators and pharmacology of visceral sensitivity: From basic to clinical investigations. Gastroenterology 112:1714 - 1743, 1997

    PubMed  Google Scholar 

  4. Besson JM, Chaouch A: Peripheral and spinal mechanisms of nociception. Physiol Rev 67:67 - 186, 1987

    PubMed  Google Scholar 

  5. Richardson BP, Engel G: The pharmacology and function of 5-HT3 receptors. Trends Neurosci 9:424 - 428, 1986

    Google Scholar 

  6. Rueff A, Dray A: 5-Hydroxytryptamine-induced sensitization and activation of peripheral fibres in the neonatal rat are mediated via different 5-hydroxytryptamine receptors. Neuroscience 50:899 - 905, 1992

    PubMed  Google Scholar 

  7. Le Bars D: Serotonin and pain. InNeuronal Serotonin. NN Osborne, M Hamon (eds). London, Wiley & Sons, 1988, pp 171 - 230

    Google Scholar 

  8. Pazos A, Hoyer D, Dietl MM, Palacios JM: Autoradiography of serotonin receptors. InNeuronal Serotonin. NN Osborne, M Hamon (eds). London, Wiley & Sons, 1988, pp 507 - 544

    Google Scholar 

  9. Hjorth S, Carlson A, Lindberg A, Sanchez D, Wikstrom H, Arvidson H, Hacksell LE, Nilsson JLG: 8-Hydroxy-2-( di-npropylamino) tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT receptor stimulating activity. J Neural Transm 55:169 - 188, 1982

    Google Scholar 

  10. Millan MJ, Bervoets K, Colpaert FC: 5-Hydroxytryptamine (5-HT)1A receptors and the tailick response. I. 8-Hydroxy-2-(di-n-propylamino)tetralin HBr-induced spontaneous tail-¯ icks in the rat as an in vivomode l of 5-HT1A re ceptor mediated activity. J Pharmacol Exp Ther256:973 - 982, 1991

    PubMed  Google Scholar 

  11. Alhenius S, Larsson K, Wijkström A: Behavioural and biochemical effects of the 5-HT1A receptor agonists fl esinoxan and 8-OH-DPAT on the rat. Eur J Pharmacol 200:259 - 266, 1991

    PubMed  Google Scholar 

  12. Fletcher A, Forster A, Bill DJ, Brown G, Cliffe IA, Hartley JE, Jones DE, McLenachan A, Stanhope KJ, Critchley DJP, et al: Electrophysiological, biochemical neurohormonal and behavioral studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist. Behav Brain Res 73:337 - 353, 1996

    PubMed  Google Scholar 

  13. Rouzade ML, Fioramonti J, Buéno L: A model for evaluation of gastric sensitivity in awake rats. Neurogastroenterol Motil 10:157 - 163, 1998

    Article  PubMed  Google Scholar 

  14. Galligan JJ, Surprenant A, Tonini M, North RA: Differential localization of 5-HT1A re ceptors on myenteric and submucosal neurons. Am J Physiol 255:G603 - G611, 1988

    PubMed  Google Scholar 

  15. Kirchgessner AL, Liu MT, Raymond JR, Gershon MD: Identi fication of cells that express 5-hydroxytryptamine 1A receptors in the nervous system of the bowel and pancreas. J Comp Neurol 364:439 - 455, 1996

    Article  PubMed  Google Scholar 

  16. Gebhart GF, Sengupta JN: Evaluation of visceral pain. InMethods in Gastrointestinal Pharmacology. TS Gaginella (ed). Boca Raton, Florida, CRC Press, 1996, pp 359 - 373

    Google Scholar 

  17. Hachet T, Caussette M: A multifunction and programmable computerized barostat. Gastroenterol Clin Biol 17:347 - 351, 1993

    PubMed  Google Scholar 

  18. Coulie B, Tack J, Janssen J: Influence of buspirone-induced fundus relaxation on the perception of gastric distension in man. Gastroenterology 112:A715, 1997

    Google Scholar 

  19. Millan MJ, Seguin L, Honoré P, Girardon S, Bervoets K: Proand antinociceptive actions of serotonin (5-HT)1A agonists and antagonists in rodents: relationship to algesiometric paradigm. Behav Brain Res 73:69 - 77, 1996

    Article  PubMed  Google Scholar 

  20. Lin Q, Peng YB, Willis WD: Antinociception and inhibition from periaqueductal gray are mediated in part by spinal 5-hydroxytryp tamine 1A receptors. J Pharmacol Exp Ther 276:958 - 967, 1996

    PubMed  Google Scholar 

  21. Daval G, Verge D, Basbaum A, Bourgoin S, Hamon M: Autoradiographic evidence of serotonin binding site on primary afferent fibers in the dorsal horn of the rat spinal cord. Neurosci Lett 83:71 - 76, 1987

    Article  PubMed  Google Scholar 

  22. Marlier L, Teilhac JR, Cerruti C, Privat A: Autoradiographic mapping of 5-HT1, 5-HT1A, 5-HT1B and 5-HT2 receptors in the rat spinal cord. Brain Res 550:15 - 23, 1991

    Article  PubMed  Google Scholar 

  23. Hunskaar S, Hole K: The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain 30:103 - 114, 1987

    PubMed  Google Scholar 

  24. Cervo L, Rossi L, Tatarczynska E, Samanin R: Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol 263:187 - 191, 1994

    PubMed  Google Scholar 

  25. Millan MJ: Serotonin and pain: Evidence that activation of 5-HT1A receptors does not elicit antinociception against noxious thermal, mechanical and chemical stimuli in mice. Pain 58:45 - 61, 1994

    PubMed  Google Scholar 

  26. Christ J, Suprenant A: Evidence that 8-hydroxy-2-( ndipropylamino)tetralin (8-OH-DPAT) is a selective a 2-adrenoceptor antagonist on guinea-pig antagonist submucous neurones. Br J Pharmacol 92:341 - 347, 1987

    PubMed  Google Scholar 

  27. Schreiber R, De Vry J: Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OHDPAT, ipsapirone and buspirone in the rat. Eur J Pharmacol 249:341 - 351, 1993

    PubMed  Google Scholar 

  28. Notivol R, Coffin B, Azpiroz F, Mearin F, Serra J, Malagelada JR: Gastric tone determine s the sensitivity of the stomach to distention. Gastroenterology 108:330 - 336, 1995

    PubMed  Google Scholar 

  29. Tack J, Coulie B, De greef T, Janssens J: Influence of sumatriptan on the perception of gastric distention in patients with functional dyspepsia. Gastroenterology 112:A304, 1997

    Google Scholar 

  30. Drossman DA, Witehead WE, Camilleri M: Irritable bowel syndrome: A technical review for practice guideline development. Gastroenterology 112:2120 - 2137, 1997

    PubMed  Google Scholar 

  31. De Vry J: 5-HT1A receptor agonists: Recent developments and controversial issues. Psychopharmacol 121:1 - 26, 1995

    PubMed  Google Scholar 

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Rouzade, ML., Fioramonti, J. & Bueno, L. Decrease in Gastric Sensitivity to Distension by 5-HT1A Receptor Agonists in Rats. Dig Dis Sci 43, 2048–2054 (1998). https://doi.org/10.1023/A:1018859214758

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