Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys

M Quik, H Cox, N Parameswaran, K O'Leary, JW Langston, D Di Monte

Ann Neurol 2007;62:588-596

Nicotine helps prevent dyskinesias and reduces the severity of pre-existing dyskinesias, according to this study.

MPTP-treated monkeys received oral nicotine or vehicle for 8 weeks prior to and then during 8 weeks of twice-daily levodopa treatment. At the end of this time, the levodopa treatment was stopped, and the nicotine/vehicle assignments were switched between groups for another 8 weeks, followed by 8 more weeks of levodopa.

In the first study period, monkeys pre-treated with nicotine had significantly less severe dyskinesias following both daily levodopa treatments, compared to those receiving vehicle. Total dyskinesia (combining duration and severity, as determined by area under the curve) was also significantly less: nicotine pretreated monkeys had between one-third and one-half as much total dyskinesia as those receiving vehicle over the course of the first 8-week period.

After crossover, during the second study period, nicotine consistently reduced dyskinesias in animals initially receiving vehicle (and that had already developed dyskinesias), by approximately 25%. Animals initially receiving nicotine developed more severe dyskinesias after switching to vehicle.

The authors suggest the effect may be mediated through nicotinic acetylcholine receptors in the striatum. They also note that sporadic nicotine delivery, as used in this study, may be more effective than continuous delivery, "because nicotinic receptors rapidly desensitize with constant exposure to nicotine, as would occur with the nicotine patch."