Body temperature dependency in baclofen-induced gastric acid secretion in rats - Relation to capsaicin-sensitive afferent neurons

Body temperature dependency in gastric functional responses to baclofen, a GABA, agonist, such as acid secretion, mucosal blood flow (GMBF) and motor activity, was examined in urethane-anesthetized rats under normal (37+/-1 d egreesC) and hypothermic (31+/-1 degreesC) conditions. A rat stomach was mo unted in an ex-vivo chamber, perfused with saline, and the acid secretion w as measured using a pH-stat method, simultaneously with GMBF by a laser Dop pler flowmeter. Gastric motility was measured using a miniature balloon as intraluminal pressure recordings. Intravenous administration of baclofen si gnificantly increased acid secretion at the doses > 0.3 mg/kg under hypothe rmic conditions, yet it caused a significant stimulation only at doses >10 mg/kg under normothermic conditions. The increases in gastric motility and GMBF were similarly induced by baclofen, irrespective of whether the animal s were subjected to normothermic or hypothermic conditions. These functiona l responses to baclofen under hypothermic conditions were totally attenuate d by either bilateral vagotomy or atropine (3 mg/kg, s.c.). Baclofen at a l ower dose (1 mg/kg i.v.) significantly increased the acid secretion even un der normothermic conditions when the animals were subjected to chemical dea fferenation of capsaicin-sensitive neurons or pretreatment with intracister nal injection of CGRP(8-37) (30 ng/rat), These results suggest that 1) gast ric effects of baclofen are dependent on body temperature in stimulating ac id secretion but not GMBF or motor activity, 2) the acid stimulatory action of baclofen is enhanced under hypothermic conditions, and 3) the suppressi on of baclofen-induced acid response under normothermic conditions may be r elated to capsaicin-sensitive afferent neuronal activity, probably mediated by central release of CGRP, (C) 2001 Elsevier Science Inc. All rights rese rved.