Chronic L-dopa (L-3,4-dihydroxyphenylalanine) is administered to recover motor function in Parkinson’s patients. However, over time, debilitating side effects occur, such as dyskinesia and mood disturbances. Some of the side effects of L-dopa have been credited to its effect on serotonin (5-HT) neurons. In this article, the authors sought to determine whether chronic L-dopa treatment decreases 5-HT neurons in the DRN and 5-HT content in forebrain regions in an oxidative stress–mediated manner. In rats treated with L-dopa for 10 days, the number of 5-HT neurons was significantly decreased in the dorsal raphe nucleus (DRN). This effect was more pronounced in the caudalextent of the dorsal DRN, a subregion found to have a significantly higher increase in the 3,4-dihydroxyphenylacetic acid/dopamine ratio in response to acute L-dopa treatment. Furthermore, pretreatment with ascorbic acid prevented the decreases in 5-HT neurons. In addition, 5-HT content was decreased significantly in the DRN and prefrontal cortex by L-dopa treatment, also prevented by ascorbic acid pretreatment. Taken together, these data illustrate that chronic L-dopa causes a 5-HT neuron loss and the depletion of 5-HT content in a subregion of the DRN as well as in the frontal cortex through an oxidative-stress mechanism.
See article at J Pharmacol Exp Ther 2014, 351:440–447.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics