Effect of baclofen on liquid and solid gastric emptying in rats

Abstract

-Context -Gamma-aminobutyric acid (GABA) is a potent inhibitory neurotransmitter. There is evidence that GABA B receptors located in the dorsal complex and in afferent fibers of the vagus nerve participate in the control of gastrointestinal motility. Objectives -To assess the intracerebroventricularly (ICV) and intravenously (IV) effect of baclofen, a GABA B receptor agonist, on liquid and solid gastric emptying in rats. Methods -Adult male Wistar rats weighing 250-300 g (n = 6-8 animals) were used. Gastric emptying of liquid test meals labeled with phenol red was evaluated by the determination of percent gastric retention (%GR) 10 and 15 min after orogastric administration of saline and 10% glucose meals, respectively. Baclofen was injected ICV (1 and 2 mg/animal) through a tube implanted into the lateral ventricle of the brain and was injected IV (1 and 2 mg/kg) into a tail vein. The gastric emptying of liquid was determined 10 or 30 min after ICV and IV baclofen administration, respectively. The gastric emptying of the solid meal was assessed by the determination of percent gastric retention 2 h after the beginning of the ingestion of the habitual ratio by the animal, consumed over a period of 30 min. Baclofen was administered ICV (1 and 2 mg/animal) or IV (1 and 2 mg/kg) immediately after the end of the ingestion of the solid meal. The control groups received vehicle (sterile saline solution) ICV or IV.Results -The group of animals receiving baclofen ICV (2 mg/animal) presented a significantly lower (P<0.05, Tukey test) %GR (mean ± SEM) of the saline (18.1 ± 2.5%) compared to control (33.2 ± 2.2%). In the group receiving the drug IV, the gastric retention of the same test meal did not differ from control. ICV and IV administration of baclofen had no effect on the gastric emptying of the 10% glucose solution compared to control. ICV administration of 1 or 2 mg baclofen/animal significantly increased the gastric retention of the solid test meal (57.9 ± 6.5% and 66.6 ± 6.3%, respectively) compared to control (35.1 ± 4.4%). The same phenomenon was observed only with the IV dose of 2 mg/kg (71.9 ± 2.6%) compared to control (52.7 ± 2.8%). Conclusions -Baclofen administered: 1. ICV (2 mg/animal), but not IV, increased gastric emptying of a non-caloric isotonic liquid test meal (saline); 2. when administered ICV or IV, it had no effect of gastric emptying of a 10% glucose solution; 3) when administered ICV (1 and 2 mg/animal) and IV (2 mg/kg) it delayed the gastric emptying of the solid meal. HEADINGS -Gastric emptying. Baclofen. Rats.

GABA‐producing Bifidobacterium dentium modulates visceral sensitivity in the intestine

“…Previous reports localized GABA A and GABA B receptors on murine and human enteric neurons, and these cells are optimally positioned to receive microbial‐derived GABA signals . As reported by other groups, this receptor distribution may coordinate GABAergic regulation of intestinal motility, gastric emptying, gastric acid secretion, and transient lower esophageal sphincter relaxation . Interestingly, a recent in vitro study showed that the GABA agonist baclofen decreased DRG neuron activity by acting on GABA B receptors and inhibiting both low‐voltage activated and high‐voltage activated Ca 2+ currents .…”

Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats

“…Steinert et al (15) reported that glutamine had no effect on antral, duodenal or pyloric pressures, or plasma cholecystokinin in healthy men, suggesting no effect on gastric emptying. On the contrary, baclofen, a GABA agonist, accelerated gastric emptying of solids but delayed emptying of liquid in 13 C-breath test in mice (16). These findings show that glutamine has differential effects on proximal and distal stomach emptying.…”