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

Abstract

Experimental cortical photothrombosis leads to pronounced alterations in the binding density of [ 3H]muscimol and [ 3H]baclofen to GABA A and GABA B receptors, both in the lesioned and the structurally intact cortex. The binding density of [ 3H]muscimol to GABA A receptors was markedly increased in the “core” of the lesion during the first week, reaching a maximum on the third day post-lesion. Simultaneously, it dropped in the exofocal primary somatosensory cortex. Reductions in the binding density of [ 3H]muscimol were also found in remote cortical areas of the contralateral hemisphere and lasted for several weeks. In contrast to the down-regulation of apparent binding density of [ 3H]muscimol, a long-lasting up-regulation of that of [ 3H]baclofen to GABA B receptors was measured in the exofocal primary somatosensory cortex and in remote cortical areas of both hemispheres. The greatest increase in the binding density of [ 3H]baclofen was seen on the seventh 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 focal ischaemic lesion. Since GABA A receptor affinity is regulated by nitric oxide, we suggest that the observed down-regulation of GABA A receptors may be correlated with a lesion-induced increase in nitric oxide, whereas the 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 hyperexcitability, is thought to be involved.