Dopamine D1-D2 Receptor Heteromer Localizes in Dynorphin/Enkephalin Neurons: INCREASED HIGH AFFINITY STATE FOLLOWING AMPHETAMINE AND IN SCHIZOPHRENIA

• Published in: The Journal of biological chemistry Vol. 285; no. 47; pp. 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: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 19.11.2010
• Subjects: Amphetamine - pharmacology; Animals; Basal Ganglia - drug effects; Basal Ganglia - metabolism; Behavior, Animal; Brain - drug effects; Brain - metabolism; Brain - pathology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Agents - pharmacology; Dynorphins - metabolism; Enkephalins - metabolism; Globus Pallidus - drug effects; Globus Pallidus - metabolism; Humans; Immunoenzyme Techniques; Male; Neurobiology; Neurons - drug effects; Neurons - metabolism; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Schizophrenia - drug therapy; Schizophrenia - metabolism; Schizophrenia - pathology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.159954

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.