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.