@article {Espinozamol.111.073304, author = {Stefano Espinoza and Ali Salahpour and Bernard Masri and Tatyana D. Sotnikova and Mirko Messa and Larry S. Barak and Marc G. Caron and Raul R. Gainetdinov}, title = {Functional interaction between Trace Amine Associated Receptor 1 (TAAR1) and dopamine D2 receptor}, elocation-id = {mol.111.073304}, year = {2011}, doi = {10.1124/mol.111.073304}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The ability of dopamine receptors to interact with other receptor subtypes may provide mechanisms for modulating dopamine-related functions and behaviors. In particular, there is evidence suggesting that the Trace Amine-Associated Receptor 1 (TAAR1) affects the dopaminergic system by regulating the firing rate of dopaminergic neurons or by altering dopamine D2 receptor (D2R) responsiveness to ligands. TAAR1 is a Gαs protein-coupled receptor that is activated by biogenic amines, "trace amines" (TAs), such as β-phenylethylamine (β-PEA) and tyramine that are normally found at low concentrations in the mammalian brain. In the present study, we investigated the biochemical mechanism of interaction between TAAR1 and D2R and the role this interaction plays in D2R-related signaling and behaviors. Using a bioluminescence resonance energy transfer (BRET) biosensor for cAMP we demonstrated that the D2R antagonists haloperidol, raclopride and amisulpride were able to enhance selectively a TAAR1-mediated β-PEA increase of cAMP. Moreover, TAAR1 and D2R were able to form heterodimers when co-expressed in HEK 293 cells and this direct interaction was disrupted in the presence of haloperidol. In addition, in mice lacking TAAR1, haloperidol-induced striatal c-Fos expression and catalepsy were significantly reduced. Taken together, these data suggest that TAAR1 and D2R have functional as well as physical interactions that could be critical for the modulation of the dopaminergic system by TAAR1 in vivo.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2011/06/15/mol.111.073304}, eprint = {https://molpharm.aspetjournals.org/content/early/2011/06/15/mol.111.073304.full.pdf}, journal = {Molecular Pharmacology} }