Amantadine attenuates response alterations resulting from repetitive L-DOPA treatment in rats

It has been shown that NMDA receptor antagonists can inhibit both the development and expression of a decrease in the duration of L-DOPA action in rats rotating after unilateral lesion of the nigro-striatal dopaminergic system. Using this model we found that the low affinity NMDA receptor antagonist amantadine (50 mg/kg b.i.d.) attenuated both the expression and development of the shortening of duration of L-DOPA (25 mg/kg b.i.d.) action. Amantadine was most efficient when given both during the induction and expression phase. However, an additional interaction experiment demonstrated that acutely given amantadine also prolongs the duration of L-DOPA-induced rotations. Hence, only the effect on development of shortening of L-DOPA action can be regarded as specific for repetitive treatment mode. The data suggest that treatment with amantadine might have beneficial effects on response fluctuations produced by chronic L-DOPA treatment.