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 GABAB 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 (Civ) or 80 mg/kg (240 μmol/kg) dipyrone (Dpiv), 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 (Cicv) or an equal volume of a solution containing 4 μmol (1333.2 μg) dipyrone (Dpicv), 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 (Dpivbac1 = 35.9% and Dpivbac2 = 26.9% vs Dpivbac0 = 51.8%). Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dpicvbac1 = 30.4% vs Dpicvbac0 = 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 GABAB receptors.38199104Weisbrodt, N.W., Gastric emptying (1997) Gastrointestinal Physiology, pp. 33-42. , Johnson LR (Editor), 5th edn. Mosby, St. Louis, MO, USAWood, J.D., Alpers, D.H., Andrews, P.L.R., Fundamentals of neurogastroenterology (1999) Gut, 45 (SUPPL. II), pp. II6-II-16Collares, E.F., Vinagre, A.M., Evidence of the effect of dipyrone on the central nervous system as a determinant of delayed gastric emptying observed in rats after its administration (2003) Brazilian Journal of Medical and Biological Research, 36, pp. 1375-1382Mody, I., De Konink, Y., Otis, T.S., Soltesz, I., Bridging the cleft at GABA synapses in the brain (1994) Trends in Neurosciences, 17, pp. 517-525Couve, A., Moss, S.J., Pangalos, M.N., GABAB receptors: A new paradigm in G protein signaling (2000) Molecular and Cellular Neurosciences, 16, pp. 296-312Johnston, G.A.R., GABAC receptors: Relatively simple transmitter-gated ion channels? (1996) Trends in Pharmacological Sciences, 17, pp. 319-323Enz, R., Cutting, G.R., Molecular composition of GABAC receptors (1998) Vision Research, 38, pp. 1431-1441Bormann, J., The 'ABC' of GABA receptors (2000) Trends in Pharmacological Sciences, 21, pp. 16-19Sivarao, D.V., Krowicki, Z.K., Hornby, P.J., Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function (1998) Neurogastroenterology and Motility, 10, pp. 305-313Greenwood-Van Meerveld, B., Barron, K.W., Tonic GABAA receptor-mediated neurotransmission in the dorsal vagal complex regulates intestinal motility in rats (1998) European Journal of Pharmacology, 346, pp. 197-202Brooks, P.A., Glaum, S.R., Miller, R.J., Spyer, K.M., The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro (1992) Journal of Physiology, 457, pp. 115-129Bertolino, M., Kellar, K.J., Vicini, S., Gillis, R.A., Nicotinic receptor mediates spontaneous GABA release in the rat dorsal motor nucleus of the vagus (1997) Neuroscience, 79, pp. 671-681Yuan, C.-S., Liu, D., Attele, A.S., GABA-ergic effects on nucleus tractus solitarius neurons receiving gastric vagal inputs (1998) Journal of Pharmacology and Experimental Therapeutics, 286, pp. 736-741Bowery, N.G., GABAB receptor pharmacology (1993) Annual Review of Pharmacology and Toxicology, 33, pp. 109-147Goto, Y., Tache, Y., Debas, H., Novin, D., Gastric acid and vagus nerve response to GABA agonist baclofen (1985) Life Sciences, 36, pp. 2471-2475Andrews, P.L.R., Wood, K.L., Systemic baclofen stimulates gastric motility and secretion via a central action in the rat (1986) British Journal of Pharmacology, 89, pp. 461-467de Groot, T., (1959) The Rat Forebrain in Stereotaxic Coordinates, , NV Noord-Holand Witgevers, Amsterdam, The NetherlandsBucaretchi, F., Collares, E.F., Effect of Phoneutria nigriventer spider venom on gastric emptying in rats (1996) Brazilian Journal of Medical and Biological Research, 29, pp. 205-211Singh, R., Ticku, M.K., Central cardiovascular effects of baclofen in spontaneously hypertensive rats (1987) Life Sciences, 40, pp. 1017-1026Bowery, N.G., Hudson, A.L., Price, G.W., GABAA and GABAB receptor site distribution in the rat central nervous system (1987) Neuroscience, 20, pp. 365-383Chu, D.C.M., Albin, R.L., Young, A.B., Penney, J.B., Distribution and kinetics of GABAB binding sites in rat central nervous system: A quantitative autoradiographic study (1990) Neuroscience, 34, pp. 341-357Misgeld, U., Bijak, M., Jarolimek, W., A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system (1995) Progress in Neurobiology, 46, pp. 423-462Scanziani, M., GABA spillover activates postsynaptic GABAB receptors to control rhythmic hippocampal activity (2000) Neuron, 25, pp. 673-681Pratt, G.D., Bowery, N.G., Autoradiography of GABA receptor binding sites in the dorsal vagal complex of the rat hindbrain (1992) British Journal of Pharmacology, 107 (SUPPL.), pp. 211P. , (Abstract)Williford, D.J., Ormsbee III, H.S., Norman, W., Harmon, J.W., Garvey III, T.Q., DiMicco, J.A., Gillis, R.A., Hindbrain GABA receptors influence parasympathetic outflow to the stomach (1981) Science, 214, pp. 193-194Herman, J.P., Cullinan, W.E., Neurocircuitry of stress: Central control of the hypothalamo-pituitary-adrenocortical axis (1997) Trends in Neurosciences, 20, pp. 78-84Bäckberg, M., Collin, M., Ovesjö, M.-L., Meister, B., Chemical coding of GABAB receptor-immunoreactive neurones in hypothalamic regions regulating body weight (2003) Journal of Neuroendocrinology, 15, pp. 1-14Kapp, B.S., Schwaber, J.S., Driscoll, P.A., The organization of insular cortex projections to the amygdaloid central nucleus and autonomic regulatory nuclei of dorsal medulla (1985) Brain Research, 360, pp. 355-360Aleksandrov, V.G., Bagaev, V.A., Nozdrachev, A.D., Panteleev, S.S., Identification of gastric related neurones in the rat insular cortex (1996) Neuroscience Letters, 216, pp. 5-8Liubashina, O., Jolkkonen, E., Pitkänen, A., Projections from the central nucleus of the amygdala to the gastric related area of the dorsal vagal complex: A Phaseolus vugaris-leucoagglutinin study in rat (2000) Neuroscience Letters, 291, pp. 85-88Liubashina, O., Bagaev, V., Khotiantsev, S., Amygdalofugal modulation of vago-vagal gastric motor reflex in the rat (2002) Neuroscience Letters, 325, pp. 183-186Doretto, M.C., Garcia-Cairasco, N., Pimenta, N.J.G., Souza, D.A., Tatsuo, M.A.K.F., Dipyrone, a novel anticonvulsant agent? Insights from three experimental epilepsy models (1998) NeuroReport, 9, pp. 2415-2421Ergün, H., Uzbay, I.T., Çelik, T., Kayir, H., Yesilyurt, Ö., Tulunay, F.C., Dipyrone inhibits ethanol withdrawal and pentylenetetrazol-induced seizures in rats (2001) Drug Development Research, 53, pp. 254-259Tossman, U., Jonsson, G., Ungerstedt, U., Regional distribution and extracellular levels of amino acids in rat central nervous system (1986) Acta Physiologica Scandinavica, 127, pp. 533-54
