Blocking the trigeminal EPSP in rat abducens motoneurons in vivo with the AMPA antagonists NBQX and GYKI 53655.
In pentobarbitone-anaesthetized rats, the effects of two AMPA receptor antagonists, the competitive antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxaline (NBQX) and the non-competitive 2,3-benzodiazepine GYKI 53655, were compared on excitatory synaptic transmission of trigeminal origin in intracellularly-recorded abducens motoneurons. The effects of both antagonists were also investigated on the alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA)-, kainate-, and N-methyl-D-aspartate (NMDA)-induced depression of extracellular antidromic field potentials in the abducens motor nucleus. Microiontophoretic application (< or =100 nA) or intravenous injection of NBQX (< or =5 mg/kg) affected both AMPA- and kainate-induced depressions whereas GYKI 53655 (< or =100 nA; < or =4 mg/kg) blocked only the AMPA-induced depression. Neither NBQX or GYKI 53655 affected NMDA-induced depressions of antidromic field potentials. Using low intravenous (i.v.) doses of the antagonists NBQX or GYKI 53655 (2-2.5 mg/kg), a complete blockade of the composite disynaptic trigeminal excitatory post-synaptic potential (EPSP) was obtained without any changes in membrane potential, input resistance and antidromic action potentials in abducens motoneurons. GYKI 53655 was more potent at low i.v. doses (0.5-1.8 mg/kg) but NBQX had longer-lasting effects. The results show the existence of differences between the blocking action of NBQX and GYKI 53655 on AMPA-mediated receptor EPSP in abducens motoneurons.
Ruiz
A
A
Unité de Neurocybernétique Cellulaire, Marseille, France.
Durand
J
J
D000010:Abducens Nerve / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001569:Benzodiazepines; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079692:GYKI 53655