title: Kindling induced by pentylenetetrazole in rats is not directly associated with changes in the expression of NMDA or benzodiazepine receptors.
abstract: Repeated injections of a subconvulsant dose of pentylenetetrazole (PTZ, 30 mg/kg IP three times weekly for 13 injections) in Wistar and hooded Lister rats resulted in kindled seizures, the extent of which varied between strains. Wistar rats achieved stage 4 of clonic-tonic seizures, whereas hooded Lister rats only reached stage 2 of convulsive waves axially through the body. Rats were killed 10 days after their final injection, and radioligand binding was used to measure the expression of NMDA receptors in cortex and hippocampus using [3H]MK-801 and [3H]L-689,560, the latter binding specifically to the NR1 subunit. [3H]Ro 15-1788 measured expression of GABA(A)-benzodiazepine binding sites containing alpha1, alpha2, alpha3, or alpha5 subunits. Specific analysis of GABA(A) receptors containing the alpha5 subunit, which are preferentially localized in the hippocampus, was assessed with [3H]L-655,708. In the cortex, there was no effect of strain or treatment on the K(D) or B(max) of any of the ligands. Similarly, there was no effect of strain or treatment on hippocampal [3H]L-689,560 or [3H]Ro 15-1788 binding. However, in the hippocampus there was a significant, albeit modest, effect of treatment on the B(max) of [3H]MK-801 binding and the B(max) and K(D) of [3H]L-655,708 binding, i.e., PTZ-treated rats had fewer [3H]MK-801 and [3H]L-655,708 binding sites (NMDA and alpha5-containing GABA(A) receptors, respectively), but, these reductions were significant only in the relatively seizure-insensitive hooded Lister strain. This suggests that the increased susceptibility to kindling in Wistar rats is not directly related to alterations in the expression of NMDA or GABA(A) receptors.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Atack
authors.forename: S M
authors.initials: SM
authors.lastname: Cook
authors.forename: P H
authors.initials: PH
authors.lastname: Hutson
authors.forename: S E
authors.initials: SE
authors.lastname: File
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors
chemical_list: D000634:Aminoquinolines; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; C105490:L 655,708; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D005442:Flumazenil; D016291:Dizocilpine Maleate; D010433:Pentylenetetrazole