Hippocampal extracellular amino acids and EEG spectral analysis in a genetic rat model of absence epilepsy.
Absence seizures have a clearly defined thalamocortical origin. However, there is evidence from a genetic rat model of absence epilepsy, GAERS, that the underlying cellular and molecular abnormalities may also manifest themselves in other brain regions. As enhanced learning has previously been associated with this rat model, we have studied extracellular amino acid levels and EEG spectra in the hippocampus of these rats, this being a brain region associated with memory and learning. We report significantly higher levels of basal extracellular glutamate within the hippocampus of GAERS, together with transient increases in citrulline and glycine following aggravation of the absence seizures with the GABA(B) agonist, (-)baclofen. Furthermore, there is a reduction in the relative power of the EEG theta frequencies in GAERS, and a slowing of the EEG following administration of (-)baclofen which is not evident in control animals. Administration of a GABA(B) antagonist, CGP 56999, at a dose which blocks absence seizures in GAERS, caused a shift to faster frequencies of the EEG in both GAERS and control rats. It is speculated that the mechanisms underlying absence seizures in GAERS may manifest themselves in other functions modulated by thalamocortical oscillations such as cognitive processing.
Richards
D A
DA
Department of Pharmacology, Division of Neuroscience, School of Medicine, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK. d.a.richards@bham.ac.uk
Morrone
L A
LA
Bowery
N G
NG
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D004832:Epilepsy, Absence / Q000235:genetics* / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; C102659:CGP 56999A; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D001418:Baclofen