The effect of age on development of abnormal involuntary movements in L-DOPA treated parkinsonian rats

Abstract

Parkinson?s disease (PD) is caused by the progressive and selective loss of dopamine-producing cells in the substantia nigra. Presentation of PD usually occurs in aging populations but can occur in younger populations as well. Continuous L-dopa therapy is currently the only viable treatment for patients with Parkinson?s disease. Unfortunately, dyskinesias (abnormal movements) occur in the majority of patients that undergo long-term dopa treatment. Understanding whether dyskinesias are a product of long-term dopa administration in the dopamine-depleted brain per se or whether other, age-related factors, are important is key to understanding dopa-induced dyskinesias. We assessed the effects of L-DOPA treatment in 4-6 month old rats and 10-11 month old rats lesioned with 6-OHDA to produce a >90% lesion of dopaminergic cells in the brain. Rats were given L-DOPA starting 5 days after an amphetamine rotation test which quantifies the extent of the lesion. Rats were scored every 3 days for 21 days using an established scoring system for abnormal involuntary movements (AIMs). We found that the extent of the lesion was a strong predictor of the development of AIMs in both the young and the aged group (100% of animals positive in the amphetamine test established AIMs, 0% of the animals negative in the amphetamine test established AIMs). The initial AIMs scores in the aged were 16.5 compared to 1.4 in the young group (unlesioned or partially lesioned animals showed 0). These data suggest that aged animals have a higher susceptibility to the development of AIMs, and more intense initial AIMs.