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

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)442-451
Number of pages10
JournalNeurotoxicity Research
Volume34
Issue number3
DOIs
StatePublished - 1 Oct 2018

Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Keywords

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

Fingerprint

Dive into the research topics of 'Identification of TAAR5 Agonist Activity of Alpha-NETA and Its Effect on Mismatch Negativity Amplitude in Awake Rats'. Together they form a unique fingerprint.

Cite this