Commentary Cellscience Reviews Vol 3 No 4 ISSN 1742-8130

Endocannabinoids get things moving in Parkinson’s disease research

Motor deficits in Parkinson’s disease reflect an imbalance in the two major pathways (direct and indirect) relaying cortical and thalamic input to basal ganglia. Kreitzer and Malenka (2007) identify unique properties of the two major subdivisions of medium spiny neurons (MSNs) in the rodent dorsal striatum, the direct-pathway and indirect-pathway MSNs. They report that only indirect-pathway MSNs released endocannabinoids as retrograde messengers that inhibited incoming glutamatergic neurotransmission from corticostriatal afferent synapses. Together with endocannabinoids, activation of dopamine D2 receptors on the indirect-pathway MSNs produced a long-term depression (LTD) of these synapses that was abolished in models of Parkinson’s disease. The LTD deficits were reversible when either a D2 agonist or an inhibitor of the endocannabinoid degrading enzyme, FAAH, were applied. Most remarkably, Parkinsonian motor deficits in the behaving animal were entirely reversed by co-administration of a D2 agonist and the FAAH inhibitor. The findings have enormous potential implications for both basic science and clinical approaches to Parkinson’s disease.

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