Neurotoxicity Research

, Volume 34, Issue 3, pp 442–451 | Cite as

Identification of TAAR5 Agonist Activity of Alpha-NETA and Its Effect on Mismatch Negativity Amplitude in Awake Rats

  • Aleksander A. Aleksandrov
  • Veronika M. KnyazevaEmail author
  • Anna B. Volnova
  • Elena S. Dmitrieva
  • Olga Korenkova
  • Stefano Espinoza
  • Andrey Gerasimov
  • Raul R. Gainetdinov


Mismatch negativity (MMN) is a well-defined component of human event-related potentials that reflects the pre-attentive, stimulus-discrimination process and is associated with involuntary switching of attention. MMN-like responses detected in animal models provide an opportunity to investigate the neural mechanisms of this process that involves several neurotransmitter and neuromodulator systems. Trace amines are believed to play a significant role in neuromodulation of synaptic transmission. The present study aimed to determine the role of trace amine-associated receptor 5 (TAAR5) in the MMN-like response in rats. First, using a bioluminescence resonance energy transfer (BRET) cAMP biosensor, we performed unbiased screening of TAAR5 ligands from a commercially available compound library (661 compounds) and identified 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA) as a potent (EC50 150 nM) TAAR5 agonist. Then, we recorded auditory event-related potentials during an oddball paradigm in awake freely moving rats that were intraperitoneally injected with a vehicle or two doses of the putative TAAR5 agonist alpha-NETA. The MMN-like response was increased by alpha-NETA 3 mg/kg dose, but not by 1 mg/kg dose or 0.9% saline solution. These results suggest that the MMN-like response in rats may be modulated, at least in part, through TAAR5-dependent processes.


Trace amine-associated receptors TAAR5 2-(Alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA) Mismatch negativity (MMN) Oddball paradigm Awake rats 


Funding Information

This study was supported by a grant from the Russian Foundation of Basic Research (Project № 17-04-00082 to AAA). BRET assay screening was supported by the Russian Science Foundation grant № 14-50-00069 to RRG and AG.

Compliance with Ethical Standards

All animal studies were carried out in strict accordance with the guidelines of the Ministry of Health of Russian Federation and the principles adopted by the FELASA and RusLASA organizations of laboratory animal use. All experiments were approved by the Saint Petersburg State University Ethical Committee for Animal Research (approval number 131-03-4). All surgical procedures were performed under anesthesia, and all efforts were made to minimize suffering.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2018_9902_MOESM1_ESM.docx (56 kb)
ESM 1 (DOCX 56 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Aleksander A. Aleksandrov
    • 1
  • Veronika M. Knyazeva
    • 1
    Email author
  • Anna B. Volnova
    • 2
  • Elena S. Dmitrieva
    • 1
  • Olga Korenkova
    • 3
  • Stefano Espinoza
    • 4
  • Andrey Gerasimov
    • 3
  • Raul R. Gainetdinov
    • 3
    • 5
  1. 1.Department of Higher Nervous Activity and PsychophysiologySaint Petersburg State UniversitySaint PetersburgRussia
  2. 2.Department of General PhysiologySaint Petersburg State UniversitySaint PetersburgRussia
  3. 3.Institute of Translational BiomedicineSaint Petersburg State UniversitySaint PetersburgRussia
  4. 4.Neuroscience and Brain TechnologiesIstituto Italiano di TecnologiaGenoaItaly
  5. 5.Skolkovo Institute of Science and Technology, SkoltechMoscowRussia

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