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Neuropharmacology. 2015 Jun;93:308-13. doi: 10.1016/j.neuropharm.2015.02.010. Epub 2015 Feb 24.

Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1.

Author information

1
Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
2
Leibniz-Institut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
3
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.
4
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.

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.

KEYWORDS:

D2 receptor; Dopamine; Striatum; TAAR1

[Indexed for MEDLINE]

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