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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 equippe d with a gastric balloon and ele ctrode s implante d in the neck muscles. Gastric distension at 15 or 20 mm Hg induced a typical posture associated with contractions of the neck muscle s. Rats received drugs 30 min before gastric distension. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) , administe red intrape ritoneally (0.5 mg/kg) incre ased gastric pain thre shold and gastric tone. These effects were reproduce d when administe red centrally (0.05 mg/kg) and blocked by intrace rebroventricular administration of the 5-HT1A antagonist WAY 100635. Flesinoxan (4 mg/kg, intrape ritone ally) , anothe r 5-HT1A agonist reproduced the effects of 8-OH-DPAT on pain thre shold and gastric tone and the a 2-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 incre ase s gastric tone and decreases gastric sensitivity to distension.
KEY WORDS: rat; gastric sensitivity; gastric distension; 5-hydroxytryptamine 1A rece ptors; 8-hydroxy-2-(di-npropylamino) tetralin; gastric volume .
Data are accumulating that functional bowel disorde rs are characte rized by visce ral hype rsensitivity. In nonulce r dyspepsia, thresholds for the perception of gastric diste nsion are lowered in comparison with he althy subje cts (1, 2). Visceral sensitivity involve s several mediators at both pe riphe ral and central levels and drugs interfering with the se mediators or their target receptors are conside red as candidate s in the treatment of patients with functional bowel disorde rs (for review, see ref. 3) .
One major function long attribute d to 5-hydroxytryptamine (5-HT) is the modulation of nociception. In the pe riphe ry, 5-HT enhance s nociceptive transmission by sensitizing nocice ptors localize d on primary afferent fibers (4 + or - 6) . In contrast, central 5-HT networks have traditionally been thought to play an opposing role and to be involve d in the induction of analge sia (4, 7) . Consistent...