Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

Abstract

Dipyrone administered intravenously (iv) or intracerebroventricularly (icv) delays gastric emptying (GE) in rats. Gamma-aminobutyric acid (GABA) is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR) of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (C iv ) or 80 mg/kg (240 µmol/kg) dipyrone (Dp iv ), followed by icv injection of 10 µl vehicle (bac0), or 0.5 (bac0.5), 1 (bac1) or 2 µg (bac2) baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (C icv ) or an equal volume of a solution containing 4 µmol (1333.2 µg) dipyrone (Dp icv ), followed by 5 µl vehicle (bac0) or 1 µg baclofen (bac1). GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%). The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors. Correspondence

Effect of 4-aminoantipyrine on gastric compliance and liquid emptying in rats

“…Additionally, it was demonstrated that the delay in GE determined by AA was blocked by the administration of bac in the CNS ( Figure 4B), as also reported for Dp (2). In the CNS, bac activates GABA B receptors, promoting modulation of neurotransmission by hyperpolarization of the postsynaptic membranes or inhibition of neurotransmitter release at the presynaptic endings (18).…”

“…Dp (Sigma, St. Louis, MO, USA), AA (Sigma) and bac (Sigma) were diluted with sterile physiological saline as a vehicle at the time of the study. The doses, in µmol, applied iv and icv were established on the basis of previous studies with Dp (1,2). GE and stomach compliance were determined after a 24-h fast, although the animals continued to receive water ad libitum up to 30 min before the studies.…”

“…When the drug was administered iv the phenomenon was abolished by vagotomy and by electrolytic lesion of the paraventricular nucleus of the hypothalamus (1). Furthermore, it was demonstrated that this effect is blocked by icv injection of baclofen (bac), a GABA B receptor agonist (2).…”

Effect of an isolated mild to moderate ischemic brain injury in the gastric emptying of liquids in rats

“…This type of injury has been selected because most of the NI children referred for antireflux surgery have either experienced perinatal hypoxic problems or have been victims of near-drowning 2 . Also, this is a well established experimental model that has been widely employed to study many different aspects of neurological diseases [11][12][13][14][15][16] .…”

“…GE was estimated indirectly by measuring percent gastric retention (%GR) of a saline test meal according to the method of Collares et al 12 as following. Every procedure was undertaken after a 22-hour fast.…”