Decreased GABA, benzodiazepine, and picrotoxinin receptor binding in brains of rats after cobalt-induced epilepsy.
In previous studies of experimental and human epilepsy, defects have been shown in the gamma-aminobutyric acid (GABA) receptors. We further investigated the role of the GABA/benzodiazepine/picrotoxinin receptor complex in the epileptic focus and also in other regions of the rat brain. The focus was induced by cobalt implantation to the right motor cortex, and the brains were dissected 16-19 days after the operation. Benzodiazepine (using [3H]flunitrazepam as a ligand; FLU), GABA [3H]muscimol; MUS), and picrotoxinin [( 35S]t-butylbicyclophosphorothionate; TBPS) receptor bindings were measured in different brain areas and the values were compared with glass-implanted controls. In the focal area, the specific receptor binding decreased in the order TBPS greater than FLU greater than MUS. In the perifocal area only TBPS binding decreased, and Scatchard analysis showed a decrease in the number of binding sites (p less than 0.05) without any effect on binding affinity. No change was seen in the binding characteristics of the other areas studied. According to our results, in cobalt-induced epilepsy the GABA/benzodiazepine/picrotoxinin receptor complex is modulated in the focal area; this may lead to a defect in chloride conductance, which in turn induces disturbed control of neuronal activity in the epileptic focus.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003035:Cobalt / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011963:Receptors, GABA-A; C037480:picrotoxinin receptor; D009118:Muscimol; D003035:Cobalt; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate