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

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, p<0.05) and memantine (170+/-264, p<0.05). SKF 38393 induced rotation tended to be potetiated by MK-801 (2451+/-741, p=0.08) and memantine (1794+/-450, p=0.21), though not statistically significant. However, LY 171555 induced rotation was reduced by MK-801 (1153+/-284, p<0.05) ad memantine (22.1+/-42.5, p<0.05). CONCLUSION: NMDA blockers act synergistically with Dl- and antagonistically with D2-mediated behavioural responses, suggesting that glutamate has different interactions with Dl- and D2 pathway.