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 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 GABAB 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.
Que
M
M
C. & O. Vogt Institute of Brain Research, Düsseldorf, Germany. que@hirn.uni-duesseldorf.de
Witte
O W
OW
Neumann-Haefelin
T
T
Schiene
K
K
Schroeter
M
M
Zilles
K
K
D000818:Animals; D001345:Autoradiography; D001418:Baclofen / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology; D007839:Functional Laterality; D018755:GABA Agonists / Q000378:metabolism / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D020767:Intracranial Thrombosis / Q000378:metabolism*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D010777:Photochemistry; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D014316:Tritium; D009118:Muscimol; D001418:Baclofen