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

5 Citations (Scopus)

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
Publication statusPublished - 1 Oct 2018

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Amines
Rats
Iodides
Evoked Potentials
Neurotransmitter Agents
Bioluminescence
Energy Transfer
Biosensing Techniques
Biosensors
Sodium Chloride
Synaptic Transmission
Energy transfer
Libraries
Screening
Animals
Animal Models
Ligands
trimethylethylammonium

Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Aleksandrov, Aleksander A. ; Knyazeva, Veronika M. ; Volnova, Anna B. ; Dmitrieva, Elena S. ; Korenkova, Olga ; Espinoza, Stefano ; Gerasimov, Andrey ; Gainetdinov, Raul R. / Identification of TAAR5 Agonist Activity of Alpha-NETA and Its Effect on Mismatch Negativity Amplitude in Awake Rats. In: Neurotoxicity Research. 2018 ; Vol. 34, No. 3. pp. 442-451.
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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.",
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Identification of TAAR5 Agonist Activity of Alpha-NETA and Its Effect on Mismatch Negativity Amplitude in Awake Rats. / Aleksandrov, Aleksander A.; Knyazeva, Veronika M.; Volnova, Anna B.; Dmitrieva, Elena S.; Korenkova, Olga; Espinoza, Stefano; Gerasimov, Andrey; Gainetdinov, Raul R.

In: Neurotoxicity Research, Vol. 34, No. 3, 01.10.2018, p. 442-451.

Research output

TY - JOUR

T1 - Identification of TAAR5 Agonist Activity of Alpha-NETA and Its Effect on Mismatch Negativity Amplitude in Awake Rats

AU - Aleksandrov, Aleksander A.

AU - Knyazeva, Veronika M.

AU - Volnova, Anna B.

AU - Dmitrieva, Elena S.

AU - Korenkova, Olga

AU - Espinoza, Stefano

AU - Gerasimov, Andrey

AU - Gainetdinov, Raul R.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

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KW - Awake rats

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KW - TAAR5

KW - Trace amine-associated receptors

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