BIHEMISPHERIC REDUCTION OF GABA(A) RECEPTOR-BINDING FOLLOWING FOCAL CORTICAL PHOTOTHROMBOTIC LESIONS IN THE RAT-BRAIN

Focal brain lesions may lead to neuronal dysfunctions in remote (exofo cal) brain regions. In the present study, focal lesions were induced i n the hindlimb representation area of the parietal cerebral cortex in rats using the technique of photothrombosis. Photothrombosis occurs af ter illumination of the brain through the intact skull following intra venous injection of the photosensitive dye Rose Bengal. This resulted in cortical lesions with a diameter of about 2 mm. Quantitative recept or autoradiography was used to study alterations in the density of [H- 3]muscimol binding sites to GABA(A) receptors seven days after lesion induction. A reduced GABA(A) receptor binding (-13 to -27% of the cont rol value) was found in layers II and III of remote exofocal regions i n the ipsi- and contralateral cortex. The reduction was consistently m ore intense in the ipsilateral cortical areas than in those of the con tralateral hemisphere. Using extracellular recordings, significant cor relations between GABA(A) receptor binding and paired pulse inhibition could be demonstrated. The present investigation demonstrates that fo cal brain lesions cause a widespread, functionally effective down-regu lation of GABA(A) receptors. These postlesional changes may result fro m lesion-induced alterations in cortical connectivity. (C) 1998 Elsevi er Science B.V. All rights reserved.