Differntial effect of NMDA antagonists on D1 & D2 mediated rotation responses in 6- hydroxydopamine (6-OHDA) lesioned rat

J Korean Neurol Assoc > Volume 15(1); 1997 > Article

Journal of the Korean Neurological Association 1997;15(1): 99-108.

6-Hydroxydopamine(6-OHDA) 파킨슨 동물모델에서 NMDA길항제가 D1및 D2에 의한 회전에 미치는 영향

홍근식, 김경문, 윤병우, 전범석

서울대학교 의대 신경과

Differntial effect of NMDA antagonists on D1 & D2 mediated rotation responses in 6- hydroxydopamine (6-OHDA) lesioned rat

Keun Sik Hong, Kyung Moon Kim, Byung Woo Yoon, and Beom S.Jeon.

Department of Neurology, Seoul National University Hospital

Abstract

Background & Objectives: Glutamate is a major neurotrammitter in corticostriatal, subthalamopallidal, and subthalamonigral pathways and interacts with other neurotrammitters. The study was done to investigate the effects of NMDA blockade on dopaminergic responses.
Methods: We made a unilateral Parkinson model in rats by injecting 6-hydroxydopamine into the substantia nigra. Rotational behavior was observed using apomorphine (mixed Dl/D2 agonist, 0. 5 mg/kg), SKF 38393 (Dl agonist, 1. 5 mg/kg), LY-171555 (D2 agonist, 0. I mg/kg), MK-801 (uncompetitive NMDA blocker, 0. 067 mg/kg), and memantine (non competitive NMDA blocker, 10 mg/kg).
Results: Contralateral rotation was induced by apomorphine (total turns for 2 hours, 1160±154), SKF 38393 (total turns for 3 hours, 1374±400), and LY 171555 (total turns for 3 hours 2316±395). NMDA antagonists per se induced mild ipsilateral rotation (MK 801; 587±131, memantine; 166+36). Apomorphine induced rotation was potentiated by MK 801 (1683±186, pConclusion: NMDA blockers act synergistically with Dl- and antagonistically with D2-mediated behavioural responses, suggesting that glutamate has different interactions with Dl- and D2 pathway.