GABA(A) receptor antagonists enhance cortical acetylcholine release induced by 5-HT(3) receptor blockade in freely moving rats.
ACh release from the rat frontal cortex was increased by both local, 0.1-1 microM, and systemic, 0.1-10 microg/kg, administration of the 5-HT(3) receptor antagonist ondansetron, reaching a maximum peak of 143% over basal values. Bicuculline, 1-10 microM, and flumazenil, 5-10 mg/kg, antagonists at different sites of the GABA(A) receptor, also enhanced ACh release, with maximum effects of 85 and 124% above baseline, respectively. GABA(A) receptor antagonists potentiated the effect induced by ondansetron on ACh release, reaching a peak increase of 238% (with bicuculline) and 259% (with flumazenil) over basal levels. These results suggest an interaction of ondansetron with GABAergic neurons modulating ACh release in the rat frontal cortex in vivo.
Diez-Ariza
Mónica
M
Department of Pharmacology, School of Medicine, University of Navarra, Irunlarrea 1, 31008, Pamplona, Spain.
García-Alloza
Mónica
M
Lasheras
Berta
B
Del Río
Joaquín
J
Ramírez
María Javier
MJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004357:Drug Synergism; D005442:Flumazenil / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D017551:Microdialysis; D009068:Movement; D017294:Ondansetron / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D005442:Flumazenil; D017294:Ondansetron; D000109:Acetylcholine; D001640:Bicuculline