The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia.
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.
Perreault
Melissa L
ML
Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Hasbi
Ahmed
A
Alijaniaram
Mohammed
M
Fan
Theresa
T
Varghese
George
G
Fletcher
Paul J
PJ
Seeman
Philip
P
O'Dowd
Brian F
BF
George
Susan R
SR
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D015259:Dopamine Agents; D004745:Enkephalins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004399:Dynorphins; D000661:Amphetamine; D004298:Dopamine