Decrease in gastric sensitivity to distension by 5-HT1A receptor agonists in rats

Dig Dis Sci. 1998 Sep;43(9):2048-54. doi: 10.1023/a:1018859214758.

Abstract

Using an in vivo model for evaluation of gastric sensitivity in awake rats, we aimed to determine whether 5-hydroxytryptamine 1A (5-HT1A) agonists modify pain threshold and gastric compliance specifically through 5-HT1A receptors. Isobaric gastric distensions were performed with a barostat using steps of 5 mm Hg in male rats equipped with a gastric balloon and electrodes implanted in the neck muscles. Gastric distension at 15 or 20 mm Hg induced a typical posture associated with contractions of the neck muscles. Rats received drugs 30 min before gastric distension. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), administered intraperitoneally (0.5 mg/kg) increased gastric pain threshold and gastric tone. These effects were reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricular administration of the 5-HT1A antagonist WAY 100635. Flesinoxan (4 mg/kg, intraperitoneally), another 5-HT1A agonist reproduced the effects of 8-OH-DPAT on pain threshold and gastric tone and the alpha2-receptor antagonist yohimbine did not modify the action of 8-OH-DPAT. Our results indicate that activation of 5-HT1A receptors at the level of the central nervous system increases gastric tone and decreases gastric sensitivity to distension.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Male
  • Pain Threshold / drug effects*
  • Piperazines / antagonists & inhibitors
  • Piperazines / pharmacology
  • Pyridines / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Serotonin Antagonists
  • Serotonin Receptor Agonists / pharmacology*
  • Stomach / chemistry
  • Stomach / drug effects*
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Yohimbine
  • flesinoxan
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin