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. The cannabinoid system seems to be involved in basal ganglia mechanisms related to motor behavior and, thus, drugs acting on cannabinoid receptors may play a role in the therapy of Parkinson?s disease. This study aims to identify and characterize the effects of CE, a cannabinoid antagonist, on motor behavioral features derived from Parkinson?s disease. In the MPTP animal model, we will examine the specific action of CE on various motor states manifested during the mimicked course of the natural disease and its chronic treatment. Specifically, we will determine: 1-the intrinsic antiparkinsonian action of CE in a dose-response curve study, 2-the magnitude of antiparkinsonian effects by comparing responses produced by different doses of CE and levodopa in a blinded trial with crossover design, 3-the synergism of CE to the levodopa action by co-administration of both drugs in a blinded controlled trial, and 4-the effects of CE on levodopa-induced dyskinesias in advanced parkinsonian monkeys that exhibit dyskinetic responses to levodopa. Subsequently and depending on the precedent results, tests of chronic treatment of CE in combination with levodopa may be included to examine tolerance. In all trials, we will assess motor behavior with the rating of motor disability and involuntary movements. This project is near to conclusion. CE has shown effects on trials of co-administration with levodopa. The drug prolongs the antiparkinsonian action of levodopa and has no worsening effects on levodopa-induced dyskinesias. We now are working on final analysis of data and preparation of publications. Proposal for continuation of studies will be submitted to further determine therapeutic applications of this drug.
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