Banerjee P K, Snead O C
Division of Neurology, Childrens Hospital of Los Angeles, University of Southern California School of Medicine 90027, USA.
Neuropharmacology. 1995 Jan;34(1):43-53. doi: 10.1016/0028-3908(94)00134-e.
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.
在大鼠中研究了丘脑N-甲基-D-天冬氨酸（NMDA）受体在实验性失神样癫痫发作产生中的可能作用。通过γ-羟基丁酸（GHB）诱导双侧同步棘波放电，并同时从不同丘脑核团以及额顶叶皮层的I-IV层进行记录。在清醒大鼠中，于给予GHB之前，向丘脑背内侧核、丘脑板内核中央外侧/中央旁核、腹后外侧核或丘脑网状核双侧注入NMDA，以剂量依赖的方式抑制了GHB诱导的棘慢波放电（SWD）。然而，当在GHB诱导的SWD发作或发展之后向上述丘脑部位注入NMDA时，未观察到对GHB诱导的SWD的这种抑制作用。用高剂量的竞争性（CGP 43487）或非竞争性NMDA受体拮抗剂（MK-801和氯胺酮）预处理也以剂量依赖的方式抑制了GHB诱导的SWD。MK-801和CGP 43487均以剂量依赖的方式拮抗NMDA介导的对GHB诱导的SWD活动的抑制，但在较低剂量时未对GHB诱导的SWD产生显著抑制。NMDA、MK-801和氯胺酮而非CGP 43487的抗SWD作用在丘脑背内侧核和板内核中比在丘脑腹后外侧核或网状核中更明显。由于低剂量的NMDA拮抗剂未能破坏GHB模型中癫痫发作的产生，这些发现不支持丘脑NMDA受体在γ-羟基丁酸诱导的失神样癫痫发病机制中的作用。
