Spatial memory improvement by levodopa in parkinsonian MPTP-treated monkeys

Abstract 

Rationale: The ameliorative effects of levodopa (l-3,4-dihydroxy-phenylalanine) on the motor impairment in Parkinson’s disease patients is well established, but characterization of its effects on the associated cognitive deficits is still incomplete. Objective: The present study determined the effect of different doses of levodopa on performance on a test of working memory in MPTP-treated rhesus monkeys, an animal model of Parkinson’s disease. Methods: Four MPTP-treated monkeys and their age-matched controls with the same experimental history as the MPTP-treated monkeys were tested on a spatial delay response task. Each daily session consisted of five trials at each of seven randomly presented delays (0, 10, 20, 30, 40, 50 and 60 s). Training was continued for 5 days in each of five different conditions. In the first condition, control and MPTP-treated animals performed the task without levodopa. In the second condition, both groups were tested with a dose of 100 mg of levodopa. In the third and fourth conditions, in which the doses of levodopa were increased to 250 and 500 mg, respectively, only the MPTP-treated animals were tested. In the final condition, the MPTP-treated animals where retested without levodopa. Results: Significant improvement was observed at all doses tested (range 100–500 mg). Conclusions: Levodopa can ameliorate memory impairments in this parkinsonian model.