GABA(A) receptor antagonists enhance cortical acetylcholine release induced by 5-HT(3) receptor blockade in freely moving rats

Brain Res. 2002 Nov 22;956(1):81-5. doi: 10.1016/s0006-8993(02)03483-2.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Bicuculline / pharmacology
  • Drug Synergism
  • Flumazenil / pharmacology
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism*
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Antagonists
  • Male
  • Microdialysis
  • Movement
  • Ondansetron / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / pharmacology*

Substances

  • GABA Antagonists
  • GABA-A Receptor Antagonists
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Flumazenil
  • Ondansetron
  • Acetylcholine
  • Bicuculline