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Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models

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  • Anatol C. Kreitzer

    (Stanford University Medical School
    University of California, San Francisco)

  • Robert C. Malenka

    (Stanford University Medical School)

Abstract

Endocannabinoid targets Imbalances in activity levels between two neuronal pathways in the brain's striatum, the 'direct' and 'indirect' motor pathways, have been proposed to underlie motor deficits seen in Parkinson's disease. A study of transgenic mice reveals important differences in the two neuronal subpopulations involved. Specifically, a prominent form of synaptic plasticity in the striatum, endocannabinoid-mediated long-term depression (eCB-LTD), is expressed only by neurons of the indirect pathway. In a mouse model of Parkinson's disease, 'rescue' of eCB-LTD by treatment with a dopamine D2 receptor agonist and an inhibitor of endocannabinoid degradation greatly improved motor performance. This suggests that a major role for dopamine in the striatum is to promote eCB-LTD at indirect pathway synapses. Drugs targeting endocannabinoid degradation could represent a novel therapeutic approach for the treatment of Parkinson's disease.

Suggested Citation

  • Anatol C. Kreitzer & Robert C. Malenka, 2007. "Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models," Nature, Nature, vol. 445(7128), pages 643-647, February.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7128:d:10.1038_nature05506
    DOI: 10.1038/nature05506
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