Premium
Long‐term depression of cortico‐striatal synaptic transmission by DHPG depends on endocannabinoid release and nitric oxide synthesis
Author(s) -
Sergeeva O. A.,
Doreulee N.,
Chepkova A. N.,
Kazmierczak T.,
Haas H. L.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05815.x
Subject(s) - metabotropic glutamate receptor , long term depression , endocannabinoid system , agonist , chemistry , pharmacology , neurotransmission , glutamate receptor , synaptic plasticity , cannabinoid receptor , neuroscience , receptor , psychology , biology , biochemistry , ampa receptor
In models of early stage Parkinson's disease (PD), motor deficits are accompanied by excessive activation of striatal glutamate receptors. Metabotropic glutamate group I receptors (mGluR I) play an important but not well‐understood role in PD progression. In mouse brain slices, bath application of the mGluR I agonist (RS)‐DHPG (3,5‐dihydroxyphenylglycine, 100 µ m for 20 min) caused a long‐term depression of corticostriatal transmission (LTD DHPG ), which was reversed by three mGluR I antagonists: LY 367385, CPCCOEt and MPEP. LTD DHPG required nitric oxide (NO) synthesis as it was blocked by the broad‐spectrum NO synthase (NOS) inhibitor N ω‐nitro‐ l ‐arginine (NL‐Arg) and impaired under blockade of neuronal NOS and in endothelial NOS‐deficient mice. Release of endocannabinoids (eCB) was critically involved in this form of striatal plasticity givem that the CB1 receptor antagonist AM251 prevented LTD DHPG , while the CB1 agonist ACEA elicited LTD. The NO synthesis necessary for LTD DHPG induction occurred downstream of CB1 activation as ACEA‐evoked LTD was also abolished by NL‐Arg. These findings are relevant for the pathophysiology of PD, as they link the overactivation of group I mGluRs and striatal NO production.