Abstract
In animal models of early Parkinson’s disease (PD), motor deficits are accompanied by excessive striatal glutamate release. Blockade of group I metabotropic glutamate receptors (mGluRs), endocannabinoid degradation and nitric oxide (NO) synthesis combats PD symptoms. Activation of group I mGluRs with the specific agonist 3,5-dihydroxyphenylglycine (DHPG) induces long-term depression of corticostriatal transmission (LTDDHPG) in the adult mouse striatum requiring NO synthesis downstream to cannabinoid CB1 receptor (CB1R) activation suggesting a dual role for LTDDHPG: neuroprotective by down-regulation of glutamatergic transmission and, under certain circumstances, neurotoxic by release of NO. We report now that LTDDHPG undergoes a developmental switch from N-methyl-D-aspartate (NMDA)-receptor-dependent/CB1R-independent to NMDA receptor-independent/CB1R-dependent plasticity with NO playing an essential role for LTDDHPG at all developmental stages. The gain in function of CB1R is explained by their developmental up-regulation evaluated with real-time reverse transcription-polymerase chain reaction. These findings are relevant for the pathophysiology and therapy of PD as they link the activation of group I mGluRs, endocannabinoid release, and striatal NO production.
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Supported by DFG SE 1768, SFB 575/3, and 8.
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Aisa N. Chepkova and Wiebke Fleischer contributed equally to the study.
An erratum to this article can be found at http://dx.doi.org/10.1007/s00424-009-0732-5
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Chepkova, A.N., Fleischer, W., Kazmierczak, T. et al. Developmental alterations of DHPG-induced long-term depression of corticostriatal synaptic transmission: switch from NMDA receptor-dependent towards CB1 receptor-dependent plasticity. Pflugers Arch - Eur J Physiol 459, 131–141 (2009). https://doi.org/10.1007/s00424-009-0714-7
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DOI: https://doi.org/10.1007/s00424-009-0714-7