Thalamic NMDA receptors in the gamma-hydroxybutyrate model of absence seizures: a cerebral microinjection study in rats.
The possible role of thalamic NMDA receptors in the generation of experimental absence-like seizures was studied in rats. Bilaterally synchronous 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 NMDA into thalamic mediodorsal nucleus, the intralaminar central lateral/paracentral nucleus, ventroposterolateral, or reticular nucleus of the thalamus in conscious rats, prior to GHB administration suppressed GHB-induced SWD in a dose dependent manner. However, no such suppression 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-competitive NMDA receptor antagonists (MK-801 and ketamine) also dose dependently suppressed GHB-induced SWD. Both MK-801 and CGP 43487 dose dependently antagonized NMDA-mediated inhibition of GHB-induced SWD activity but at lower doses did not produce significant inhibition of GHB-induced SWD. The anti-SWD effects of NMDA, MK-801 and ketamine but not 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 the generation of seizures in the GHB model, these findings do not support a role for thalamic NMDA receptors in the pathogenesis of absence-like seizures induced by gamma-hydroxybutyric acid.
Banerjee
P K
PK
Division of Neurology, Childrens Hospital of Los Angeles, University of Southern California School of Medicine 90027, USA.
Snead
O C
OC
D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000139:chemically induced*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013788:Thalamus / Q000187:drug effects*; D013997:Time Factors
D006885:Hydroxybutyrates; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate