Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous absence epilepsy: a microdialysis study.
There is compelling evidence that excessive GABA-mediated inhibition may underlie the abnormal electrical activity, initiated in the thalamus, associated with epileptic absence seizures. In particular, the GABAB receptor subtype seems to play a critical role, because its antagonists are potent inhibitors of absence seizures, whereas its agonists exacerbate seizure activity. Using a validated rat model of absence epilepsy, we have previously found no evidence of abnormal GABAB receptor density or affinity in thalamic tissue. In the present study, we have used in vivo microdialysis to monitor changes in levels of extracellular GABA and other amino acids in this brain region. We have shown that basal extracellular levels of GABA and, to a lesser extent, taurine are increased when compared with values in nonepileptic controls. However, modifying GABAergic transmission with the GABAB agonist (-)-baclofen (2 mg/kg i.p.), the GABAB antagonist CGP-35348 (200 mg/kg i.p.), or the GABA uptake inhibitor tiagabine (100 microM) did not produce any further alteration in extracellular GABA levels, despite the ability of these compounds to increase (baclofen and tiagabine) or decrease (CGP-35348) seizure activity. These findings suggest that the increased basal GABA levels observed in this animal model are not simply a consequence of seizure activity but may contribute to the initiation of absence seizures.
Richards
D A
DA
Department of Pharmacology, School of Pharmacy, London, England.
Lemos
T
T
Whitton
P S
PS
Bowery
N G
NG
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000378:metabolism* / Q000503:physiopathology; D005110:Extracellular Space / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D017551:Microdialysis; D009557:Nipecotic Acids / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism*; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D009557:Nipecotic Acids; D009943:Organophosphorus Compounds; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen; D011188:Potassium; D000078308:Tiagabine