The Dopamine D1-D2 Receptor Heteromer Localizes in Dynorphin/Enkephalin Neurons

The distribution and function of neurons coexpressing the dopamine D1 and D2 receptors in the basal ganglia and mesolimbic system are unknown. We found a subset of medium spiny neurons coexpressing D1 and D2 receptors in varying densities throughout the basal ganglia, with the highest incidence in n...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-11, Vol.285 (47), p.36625-36634
Main Authors: Perreault, Melissa L., Hasbi, Ahmed, Alijaniaram, Mohammed, Fan, Theresa, Varghese, George, Fletcher, Paul J., Seeman, Philip, O'Dowd, Brian F., George, Susan R.
Format: Article
Language:English
Subjects:
AMPA Receptor
Amphetamine
Calcium/Calmodulin-dependent Protein Kinase (CaMK)
Dopamine D1-D2 Receptor Heteromer
G Protein-coupled Receptors (GPCR)
Neurological Diseases
Neuropeptide
Neuroscience
Nucleus Accumbens
Schizophrenia
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Summary:The distribution and function of neurons coexpressing the dopamine D1 and D2 receptors in the basal ganglia and mesolimbic system are unknown. We found a subset of medium spiny neurons coexpressing D1 and D2 receptors in varying densities throughout the basal ganglia, with the highest incidence in nucleus accumbens and globus pallidus and the lowest incidence in caudate putamen. These receptors formed D1-D2 receptor heteromers that were localized to cell bodies and presynaptic terminals. In rats, selective activation of D1-D2 heteromers increased grooming behavior and attenuated AMPA receptor GluR1 phosphorylation by calcium/calmodulin kinase IIα in nucleus accumbens, implying a role in reward pathways. D1-D2 heteromer sensitivity and functional activity was up-regulated in rat striatum by chronic amphetamine treatment and in globus pallidus from schizophrenia patients, indicating that the dopamine D1-D2 heteromer may contribute to psychopathologies of drug abuse, schizophrenia, or other disorders involving elevated dopamine transmission.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110.159954