THALAMIC NMDA RECEPTORS IN THE GAMMA-HYDROXYBUTYRATE MODEL OF ABSENCESEIZURES - A CEREBRAL MICROINJECTION STUDY IN RATS

The possible role of thalamic NMDA receptors in the generation of expe rimental absence-like seizures was studied in rats. Bilaterally synchr onous spike wave discharges were induced by gamma-hydroxybutyric acid (GHB) and were recorded simultaneously from different thalamic nuclei and the layers I-IV of frontoparietal cortex. Bilateral infusions of N MDA into thalamic mediodorsal nucleus, the intralaminar central latera l/paracentral nucleus, ventroposterolateral, or reticular nucleus of t he thalamus in conscious rats, prior to GHB administration suppressed GHB-induced SWD in a dose dependent manner. However, no such suppressi on of GHB-induced SWD was observed when NMDA infusions were made into the above thalamic sites after the onset or development of GHB-induced SWD. Pretreatment with high doses of competitive (CGP 43487) or non-c ompetitive NMDA receptor antagonists (MK-801 and ketamine) also dose d ependently suppressed GHB-induced SWD. Both MK-801 and CGP 43487 dose dependently antagonized NMDA-mediated inhibition of GHB-induced SWD ac tivity but at lower doses did not produce significant inhibition of GH B-induced SWD. The anti-SWD effects of NMDA, MK-801 and ketamine but n ot CGP 43487 were more pronounced in the mediodorsal and intralaminar thalamic nuclei than in the ventroposterolateral or reticular nucleus of thalamus. Because low doses of NMDA antagonists failed to disrupt t he generation of seizures in the GHB model, these findings do not supp ort a role for thalamic NMDA receptors in the pathogenesis of absence- like seizures induced by gamma-hydroxybutyric acid.