Changes in GABA(A) and GABA(B) receptor binding following cortical photothrombosis: A quantitative receptor autoradiographic study

Experimental cortical photothrombosis leads to pronounced alterations in th e binding density of [H-3]muscimol and [H-3]baclofen to GABA(A) and GABA(B) receptors, both in the lesioned and the structurally intact cortex. The bi nding density of [H-3]muscimol to GABA(A) receptors was markedly increased in the "core" of the lesion during the first week, reaching a maximum on th e third day post-lesion. Simultaneously, it dropped in the exofocal primary somatosensory cortex. Reductions in the binding density of [H-3]muscimol w ere also found in remote cortical areas of the contralateral hemisphere and lasted for several weeks. In contrast to the down-regulation of apparent b inding density of [H-3]muscimol, a long-lasting up-regulation of that of [H -3]baclofen to GABA(B) receptors was measured in the exofocal primary somat osensory cortex and in remote cortical areas of both hemispheres. The great est increase in the binding density of [H-3]baclofen was seen on the sevent h day in the surroundings of the lesion. Our findings indicate that widespread alterations in the concentrations of GABA(A) and GABA(B) receptors are induced in remote cortical areas by a foc al ischaemic lesion. Since GABA(A) receptor affinity is regulated by nitric oxide, we suggest that the observed down-regulation of GABA(A) receptors m ay be correlated with a lesion-induced increase in nitric oxide, whereas th e up-regulation of GABA(B) receptors might be caused by other mechanisms, e .g., compensatory processes. In the centre of the lesion, however, a GABA(A ) receptor-mediated mechanism, which limits the spread of lesion-induced hy perexcitability, is thought to be involved. (C) 1999 IBRO. Published by Els evier Science Ltd.