title: Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1.
abstract: Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) known to modulate dopaminergic system through several mechanisms. Mice lacking this receptor show a higher sensitivity to dopaminergic stimuli, such as amphetamine; however, it is not clear whether D1 or D2 dopamine receptors and which associated intracellular signaling events are involved in this modulation. In the striatum of TAAR1 knock out (TAAR1-KO mice) we found that D2, but not D1, dopamine receptors were over-expressed, both in terms of mRNA and protein levels. Moreover, the D2 dopamine receptor-related G protein-independent AKT/GSK3 signaling pathway was selectively activated, as indicated by the decrease of phosphorylation of AKT and GSK3β. The decrease in phospho-AKT levels, suggesting an increase in D2 dopamine receptor activity in basal conditions, was associated with an increase of AKT/PP2A complex, as revealed by co-immunoprecipitation experiments. Finally, we found that the locomotor activation induced by the D2 dopamine receptor agonist quinpirole, but not by the full D1 dopamine receptor agonist SKF-82958, was increased in TAAR1-KO mice. These data demonstrate pronounced supersensitivity of postsynaptic D2 dopamine receptors in the striatum of TAAR1-KO mice and indicate that a close interaction of TAAR1 and D2 dopamine receptors at the level of postsynaptic structures has important functional consequences.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Espinoza
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ghisi
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Emanuele
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Damiana
authors.initials: D
authors.lastname: Leo
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Ilya
authors.initials: I
authors.lastname: Sukhanov
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Tatiana D
authors.initials: TD
authors.lastname: Sotnikova
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
authors.forename: Evelina
authors.initials: E
authors.lastname: Chieregatti
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia; Skolkovo Institute of Science and Technology (Skoltech) Skolkovo, Moscow Region 143025, Russia. Electronic address: raul.gainetdinov@iit.it.
authors.forename: Raul R
authors.initials: RR
authors.lastname: Gainetdinov
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D000095383:Trace Amine-Associated Receptors
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D051057:Proto-Oncogene Proteins c-akt; D019257:Quinpirole; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C071262:SK&F 82958
keywords: D2 receptor; Dopamine; Striatum; TAAR1