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Activation of calcium/calmodulin-dependent protein kinase IIalpha in the striatum by the heteromeric D1-D2 dopamine receptor complex.
- Source :
-
Neuroscience [Neuroscience] 2010 Jan 20; Vol. 165 (2), pp. 535-41. - Publication Year :
- 2010
-
Abstract
- Synaptic plasticity in the striatum is a key mechanism that underlies processes such as reward related incentive learning and behavioral habit formation resulting from drugs of abuse. Key aspects of these functions are dependent on dopamine transmission as well as activation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha). In this study, we examined the ability of a recently identified heteromeric complex composed of D1 and D2 dopamine receptors coupled to Gq/11 to activate striatal CaMKIIalpha. Using the dopaminergic agonist SKF83959, which selectively activates the D1-D2 complex, we demonstrated phosphorylation of CaMKIIalpha at threonine 286, both in heterologous cells and in the murine striatum in vivo. Phosphorylation of CaMKIIalpha by activation of the receptor complex required concurrent agonism of both D1 and D2 receptors and was independent of receptor pathways that modulated adenylyl cyclase. The identification of this novel mechanism by which dopamine may modulate synaptic plasticity has implications for our understanding of striatal-mediated reward and motor function, as well as neuronal disorders in which striatal dopaminergic neurotransmission is involved.
- Subjects :
- Adenylyl Cyclases metabolism
Animals
Cell Line
Corpus Striatum drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
Receptors, Dopamine D1 agonists
Receptors, Dopamine D1 genetics
Receptors, Dopamine D2 agonists
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate metabolism
Signal Transduction
Synaptic Transmission drug effects
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Corpus Striatum physiology
GTP-Binding Protein alpha Subunits, Gq-G11 metabolism
Receptors, Dopamine D1 metabolism
Receptors, Dopamine D2 metabolism
Synaptic Transmission physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 165
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19837142
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2009.10.017