Narrow beneficial effect of dextromethorphan on levodopa-induced motor response alterations in an experimental model of parkinsonism

The effects of acute and chronic dextromethorphan on levodopa-induced motor response alterations have been studied in rats with unilateral lesion of n igrostriatal pathway induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Da wley rats received a 6-OHDA injection (8 mu g) into the left medial forebra in bundle. To validate the effect of acute dextromethorphan administration, groups of rats were treated with levodopa (25 mg/kg, twice daily) for 22 d ays. On day 23, animals received dextromethorphan (20, 30 or 40 mg/kg) imme diately before levodopa. In a second set of experiments, lesioned rats were concomitantly treated with levodopa plus dextromethorphan (20, 30 or 40 mg /kg, twice at day) for 22 consecutive days in order to investigate the pote ntial effect of chronic dextromethorphan administration in preventing the d ecrease in the duration of motor response. As expected, the duration of the motor response to levodopa had significantly decreased by the 22nd day of levodopa in each group of treatment. Acute administration of dextromethorph an on day 23 reversed the reduction in the duration of the levodopa respons e only when administered at the lowest dose used in the present study (20 m g/kg) (p < 0.05). Chronic administration of dextromethorphan concomitant to levodopa did not prevent levodopa effect showing a significant decrease on motor response duration (124 +/- 4 on day 1 vs. 88 +/- 16 on day 22, p < 0 .05, 30 mg/kg, twice a day). Our results indicate that in parkinsonian rats dextromethorphan is not a useful drug to prevent levodopa-induced motor al terations, however, low doses of dextromethorphan may be beneficial to reve rse these alterations in motor response. (C) 1999 Elsevier Science B.V. All rights reserved.