EXTRACELLULAR GABA IN THE VENTROLATERAL THALAMUS OF RATS EXHIBITING SPONTANEOUS ABSENCE EPILEPSY - A MICRODIALYSIS STUDY

There is compelling evidence that excessive GABA-mediated inhibition m ay underline the abnormal electrical activity, initiated in the thalam us, associated with epileptic absence seizures. In particular, the GAB AB receptor subtype seems to play a critical role, because its antagon ists are potent inhibitors of absence seizures, whereas its agonists e xacerbate seizure activity. Using a validated rat model of absence epi lepsy, we have previously found no evidence of abnormal GABA, receptor density or affinity in thalamic tissue. in the present study, we have used in vivo microdialysis to monitor changes in levels of extracellu lar GABA and other amino acids in this brain region. We have shown tha t basal extracellular levels of GABA and, to a lesser extent, taurine are increased when compared with values in nonepileptic controls. Howe ver, modifying GABAergic transmission with the GABAB agonist (-)-baclo fen (2 mg/kg i.p.), the GABA, antagonist CGP-35348 (200 mg/kg i.p.), o r the GABA uptake inhibitor tiagabine (100 mu M) did not produce any f urther 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 ba sal GABA levels observed in this animal model are not simply a consequ ence of seizure activity but may contribute to the initiation of absen ce seizures.