Transient up-regulation of gamma-aminobutyric acid(A) receptor binding by lubeluzole after neocortical specify lesion in rats

The effect of the neuroprotective drug lubeluzole on cortical receptor bind ing was investigated in animals with photothrombotic ischemic lesions. Cont rol animals were treated with the inactive stereoisomer of the drug. Lubelu zole was applied intravenously as a single bolus (0.31 mg/kg) followed by a 1-h infusion of 0.31 mg/kg. Lubeluzole selectively increased gamma -amino- butyric acid(A) (GABA(A)) receptor binding but had no significant and/or co nsistent effects on N-methyl-D-aspartate (NMDA), (+/-)-alpha -amino-3-hydro xy-5-methylisoxazole-4-propionic acid (AMPA), and kainate receptors. Lubelu zole caused a significant up-regulation of GABA(A) receptor binding in the lesioned area as well as in unimpaired cortical areas of both hemispheres. This effect appeared in the hours following the lesion and peaked at 24 h. Our findings suggest that reduced cortical excitability brought about by in creased binding capacities of GABA(A) receptors may contribute to the neuro protective effect of lubeluzole. (C) 2000 Published by Elsevier Science Ire land Ltd.