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 nigrostriatal pathway induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a 6-OHDA injection (8 microg) into the left medial forebrain bundle. To validate the effect of acute dextromethorphan administration, groups of rats were treated with levodopa (25 mg/kg, twice daily) for 22 days. On day 23, animals received dextromethorphan (20, 30 or 40 mg/kg) immediately 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 potential effect of chronic dextromethorphan administration in preventing the decrease 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 dextromethorphan on day 23 reversed the reduction in the duration of the levodopa response only when administered at the lowest dose used in the present study (20 mg/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 alterations, however, low doses of dextromethorphan may be beneficial to reverse these alterations in motor response.