GABAA receptor impairment in the genetic absence epilepsy rats from Strasbourg (GAERS): an immunocytochemical and receptor binding autoradiographic study

Abstract Some aspects of the GABA and cholinergic systems have been investigated in the cortex and thalamus of GAERS Wistar rats, a model of petit-mal epilepsy, and in a non-epileptic control strain. GABA and its synthetic enzyme, glutamic acid decarboxylase (GAD), were located by immunocytochemistry; the GABA A receptors were evaluated by autoradiography of GABA-enhanced 3 H-flunitrazepam binding and by immunocytochemistry using specific antibodies against the β 2 -β 3 subunits of GABAP A receptor protein. GABA and GAD immunocytochemistry did not show up any difference in density or distribution of immunoreactive elements (fibers, terminals and neurons) between epileptic and control animals, but autoradiographic and immunocytochemical studies showed a decreased enhancement of 3 H-flunitrazepam binding and of β 2 -β 3 subunits of GABA A receptor in the sensorimotor cortex and anterior thalamic areas of the epileptic strain. No differences were found in benzodiazepine receptors in the two strains. GABA B receptors were measured as 3 H-baclofen binding in a crude synaptic membrane preparation and there was no difference between epileptic and control animals. Choline acetyltransferase, the synthetic enzyme for acetylcholine, and muscarinic receptor subtypes (M 1 and M 2 ), visualized respectively by an immunocytochemical procedure and binding autoradiography, did not differ in epileptic and normal rats. The data suggest an impairment of the ‘GABA A system’ in restricted brain regions of epileptic rats, due to a reduction of receptor β 2 -β 3 subunits and coupling to benzodiazepine receptors despite the normal synthesis and location of the neurotransmitter.