Pentylenetetrazol kindling decreases N-methyl-D-aspartate and kainate but increases gamma-aminobutyric acid-A receptor binding in discrete rat brain areas.
Pentylenetetrazol is a convulsive drug acting on gamma-aminobutyric acid-A (GABA[A]) gated-chloride receptors. In this study we used a subconvulsive dose (30 mg/kg) of pentylenetetrazol to induce a fully kindled state in rats. Glutamate receptors were evaluated using [3H]-[1(2-thienylcyclohexyl)]-piperidin (TCP) and [3H]kainate receptor autoradiography and [3H]muscimol autoradiography was used to study GABA(A) receptors. In fully kindled rats decreased N-methyl-D-aspartate receptor binding was found in parietal cortex, area CA2 of hippocampus and piriform cortex. Decreased kainate receptor binding was observed in all areas of the hippocampus, the medial amygdala and in the piriform cortex in the kindled rats. In contrast, GABA(A) receptor binding increased in the dentate gyrus. It is concluded that modulatory neuronal plasticity events are induced in fully pentylenetetrazol kindled rats, which appears to lead to decreased glutamatergic excitation and increased GABAergic inhibition in brain regions implicated in the development of seizure activity.
Luthman
J
J
Department Biochemistry, Preclinical Research and Development, Södertälje, Sweden.
Humpel
C
C
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003292:Convulsants; D005260:Female; D007696:Kindling, Neurologic; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D003292:Convulsants; D010433:Pentylenetetrazole; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate