Decrease in gastric sensitivity to distension by 5-HT1A receptor agonists in rats.
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.
Rouzade
M L
ML
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
Fioramonti
J
J
Bueno
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013270:Stomach / Q000737:chemistry / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015016:Yohimbine; C056895:flesinoxan; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin