DEVELOPMENT OF A MONKEY DYSTONIA MODEL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These studies are designed to assess the effects of dopamine depletion in infant monkeys. Based on clinical observations, these experiments test the hypothesis that such depletion may result not in parkinsonism (as in older animals), but in dystonia. During the reporting period, we continued observations in three infant Rhesus monkeys which were treated with weekly injections of MPTP. The animals tolerated these injections very well and continued to gain weight. Despite the fact that the cumulative MPTP doses surpassed those used in older animals for the induction of parkinsonism threefold, the animals did not develop significant parkinsonism or dystonia. We also added two young animals which were treated with a higher dose of MPTP over the course of one month. At this time, one of the animals developed neck dystonia (and parkinsonism), while the other one is still normal. These results provided evidence that a low rate of dopamine depletion is not sufficient to produce dystonia in young individuals, but that other factors, such as abnormal plasticity, need to come into play as well. However, more severe dopamine depletion in very young animals may produce dystonia. We plan to carry out further anatomical studies in the future to examine the pattern of dopamine loss induced by the treatment, and delineate the treatment conditions that result in dystonia.