2-B-P-101
<title_ja>レボドパ誘発ジスキネジアラットモデルにおけるレボドパによる線条体GABA濃度上昇はNR2B/NMDA受容体遮断薬Ro25-6981により抑制される</title_ja>
<title_en>Ro25-6981, an NR2B/NMDA receptor antagonist, inhibits <i>l</i>-DOPA-induced striatal GABA release in the<i> l</i>-DOPA-induced dyskinesia model rats.</title_en>
〇大山 祥延、上園 崇、森 麻美、恒岡 弥生、坂本 謙司
Ohyama Yoshinobu, Takashi Uezono, Asami Mori, Yayoi Tsuneoka, Kenji Sakamoto
帝京大・薬・医薬品作用
Lab. Med. Pharmacol., Fac. Pharma-Sci., Teikyo Univ.
In the l-DOPA-induced dyskinesia model rats, direct striatopallidal GABAergic neurons respond excessively to l-DOPA. NMDA receptors modulating corticostriatal glutamatergic-dopaminergic interactions have been shown to be important players in LID. In this study, we examined the effect of Ro25-6981, an NR2B-containing NMDA (NR2B/NMDA) receptor antagonist, on l-DOPA-induced striatal GABA release in the LID model rats using in vivo microdialysis.
Unilaterlly 6-hydroxydopamine-lesioned rats were primed with l-DOPA/benserazide for three weeks. l-DOPA/benserazide p.o.administration elevated striatal GABA level in the LID model rats. This elevation was maintained over three hours and enhanced by the perfusion of 1(S),9(R)-(-)-bicuculline methiodide, a GABAA receptor antagonist, through the probe implanted in striatum. On the other hand, this elevation of striatal GABA level was completely abolished when Ro25-6981 was perfused in striatum.
These results suggest that the abnormal activity of striatal GABA neurons is modulated via NR2B/NMDA receptors in the l-DOPA-induced dyskinesia model rats.