Relevant conflicts of interest/financial disclosures: Nothing to report.
Nicotine reduces established levodopa-induced dyskinesias in a monkey model of Parkinson's disease
Article first published online: 8 JUL 2013
© 2013 International Parkinson and Movement Disorder Society
Volume 28, Issue 10, pages 1398–1406, September 2013
How to Cite
Quik, M., Mallela, A., Ly, J. and Zhang, D. (2013), Nicotine reduces established levodopa-induced dyskinesias in a monkey model of Parkinson's disease. Mov. Disord., 28: 1398–1406. doi: 10.1002/mds.25594
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 23 SEP 2013
- Article first published online: 8 JUL 2013
- Manuscript Accepted: 31 MAY 2013
- Manuscript Revised: 17 MAY 2013
- Manuscript Received: 27 MAR 2013
- nonhuman primate;
- Parkinson's disease
Although 3,4-dihydroxyphenylalanine (levodopa) is the gold-standard treatment for Parkinson's disease, it can lead to disabling dyskinesias. Previous work demonstrated that nicotine reduces levodopa-induced dyskinesias (LIDs) in several parkinsonian animal models. The goal of this study was to determine whether the duration of nicotine administration affects its ability to reduce LIDs in levodopa-primed and levadopa-naíve monkeys and also to test whether tolerance develops to the beneficial effects of nicotine. Monkeys were injected with MPTP (1.9-2.0 mg/kg subcutaneously) over 3 to 5 months until parkinsonism developed. Nicotine (300 μg/mL) was administered in drinking water (over 4–6 months) to levodopa-primed or levodopa-naíve monkeys, with levodopa/carbidopa (10/2.5 mg/kg) gavaged twice daily. One set of MPTP-lesioned monkeys (n = 23) was first gavaged with levodopa and subsequently received nicotine 4 weeks later, when dyskinesias plateaued, or 8 weeks later, when dyskinesias were established. A 60% to 70% decrease in LIDs was observed after several weeks of nicotine treatment in both groups. A second set of monkeys (n = 26) received nicotine 8 or 2 weeks before levodopa. In the 8-week nicotine pretreatment group, there was an immediate reduction in LIDs, which plateaued at 60% to 70%. In the 2-week nicotine pretreatment group, there were initial small decreases in LIDs, which plateaued at 60% to 70% several weeks later. Thus, nicotine pretreatment and nicotine post-treatment were similarly efficacious in reducing LIDs. The beneficial effect of nicotine persisted throughout the study (17–23 weeks). Nicotine did not worsen parkinsonism. These data suggest that nicotine treatment has potential as a successful antidyskinetic therapy for patients with Parkinson's disease. © 2013 International Parkinson and Movement Disorder Society