GABA(A) RECEPTOR IMPAIRMENT IN THE GENETIC ABSENCE EPILEPSY RATS FROMSTRASBOURG (GAERS) - AN IMMUNOCYTOCHEMICAL AND RECEPTOR-BINDING AUTORADIOGRAPHIC STUDY

Some aspects of the GABA and cholinergic systems have been investigate d in the cortex and thalamus of GAERS Wistar rats, a model of petit-ma l epilepsy, and in a non-epileptic control strain. GABA and its synthe tic enzyme, glutamic acid decarboxylase (GAD), were located by immunoc ytochemistry; the GABA(A) receptors were evaluated by autoradiography of GABA-enhanced H-3-flunitrazepam binding and by immunocytochemistry using specific antibodies against the beta2-beta3 subunits of GABA(A) receptor protein. GABA and GAD immunocytochemistry did not show up any difference in density or distribution of immunoreactive elements (fib ers, terminals and neurons) between epileptic and control animals, but autoradiographic and immunocytochemical studies showed a decreased en hancement of H-3-flunitrazepam binding and of beta2-beta3 subunits of GABA(A) receptor in the sensorimotor cortex and anterior thalamic area s of the epileptic strain. No differences were found in benzodiazepine receptors in the two strains. GABA(B) receptors were measured as H-3- baclofen binding in a crude synaptic membrane preparation and there wa s no difference between epileptic and control animals. Choline acetylt ransferase, the synthetic enzyme for acetylcholine, and muscarinic rec eptor subtypes (M1 and M2), visualized respectively by an immunocytoch emical procedure and binding autoradiography, did not differ in epilep tic and normal rats. The data suggest an impairment of the 'GABA(A) sy stem' in restricted brain regions of epileptic rats, due to a reductio n of receptor beta2-beta3 subunits and coupling to benzodiazepine rece ptors despite the normal synthesis and location of the neurotransmitte r.