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.
Similar content being viewed by others
REFERENCES
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
Coffin B, Azpiroz F, Guarner F, Malagelada JR: Selective gastric hypersensitivity and reflex hyporeactivity in functional dyspepsia. Gastroenterology 107:1345 - 1351, 1994
Bueno L, Fioramonti J, Delvaux M, Frexinos J: Mediators and pharmacology of visceral sensitivity: From basic to clinical investigations. Gastroenterology 112:1714 - 1743, 1997
Besson JM, Chaouch A: Peripheral and spinal mechanisms of nociception. Physiol Rev 67:67 - 186, 1987
Richardson BP, Engel G: The pharmacology and function of 5-HT3 receptors. Trends Neurosci 9:424 - 428, 1986
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
Le Bars D: Serotonin and pain. InNeuronal Serotonin. NN Osborne, M Hamon (eds). London, Wiley & Sons, 1988, pp 171 - 230
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
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
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
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
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
Rouzade ML, Fioramonti J, Buéno L: A model for evaluation of gastric sensitivity in awake rats. Neurogastroenterol Motil 10:157 - 163, 1998
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
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
Gebhart GF, Sengupta JN: Evaluation of visceral pain. InMethods in Gastrointestinal Pharmacology. TS Gaginella (ed). Boca Raton, Florida, CRC Press, 1996, pp 359 - 373
Hachet T, Caussette M: A multifunction and programmable computerized barostat. Gastroenterol Clin Biol 17:347 - 351, 1993
Coulie B, Tack J, Janssen J: Influence of buspirone-induced fundus relaxation on the perception of gastric distension in man. Gastroenterology 112:A715, 1997
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
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
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
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
Hunskaar S, Hole K: The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain 30:103 - 114, 1987
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
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
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
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
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
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
Drossman DA, Witehead WE, Camilleri M: Irritable bowel syndrome: A technical review for practice guideline development. Gastroenterology 112:2120 - 2137, 1997
De Vry J: 5-HT1A receptor agonists: Recent developments and controversial issues. Psychopharmacol 121:1 - 26, 1995
Rights and permissions
About this article
Cite this article
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
Issue Date:
DOI: https://doi.org/10.1023/A:1018859214758