TY - JOUR

T1 - Trace Amine-Associated Receptor 1 Agonist Modulates Mismatch Negativity-Like Responses in Mice

AU - Aleksandrov, A.A.

AU - Knyazeva, V.M.

AU - Volnova, A.B.

AU - Dmitrieva, E.S.

AU - Polyakova, N.V.

AU - Gainetdinov, R.R.

N1 - Publisher Copyright: © 2007 - 2019 Frontiers Media S.A. All Rights Reserved.

PY - 2019/5/3

Y1 - 2019/5/3

N2 - The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor widely expressed in the mammalian brain, particularly in limbic system and monoaminergic areas. It has proven to be an important modulator of dopaminergic, serotoninergic and glutamatergic neurotransmission and is considered to be a potential useful target for the pharmacotherapy of neuropsychiatric disorders, including schizophrenia. One of the promising schizophrenia endophenotypes is a deficit in neurocognitive abilities manifested as mismatch negativity (MMN) deficit. This study examines the effect of TAAR1 partial agonist RO5263397 on the MMN-like response in freely moving C57BL/6 mice. Event-related potentials (ERPs) were recorded from awake mice in the oddball paradigm before and after RO5263397 administration. The RO5263397 (but not saline) administration increased the N40 amplitude in response to deviant stimuli. That provided the MMN-like difference at the 36-44 ms interval after the injection. The pitch deviance-elicited changes before the injection and in the control paradigm were established for the Р68 component. After TAAR1 agonist administration the P68 amplitude in response both to standard and deviant stimuli was increased. These results suggest that the MMN-like response in mice may be modulated through TAAR1-dependent processes (possibly acting through the direct or indirect NMDA modulation), indicating the TAAR1 agonists potential antipsychotic and pro-cognitive activity.

AB - The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor widely expressed in the mammalian brain, particularly in limbic system and monoaminergic areas. It has proven to be an important modulator of dopaminergic, serotoninergic and glutamatergic neurotransmission and is considered to be a potential useful target for the pharmacotherapy of neuropsychiatric disorders, including schizophrenia. One of the promising schizophrenia endophenotypes is a deficit in neurocognitive abilities manifested as mismatch negativity (MMN) deficit. This study examines the effect of TAAR1 partial agonist RO5263397 on the MMN-like response in freely moving C57BL/6 mice. Event-related potentials (ERPs) were recorded from awake mice in the oddball paradigm before and after RO5263397 administration. The RO5263397 (but not saline) administration increased the N40 amplitude in response to deviant stimuli. That provided the MMN-like difference at the 36-44 ms interval after the injection. The pitch deviance-elicited changes before the injection and in the control paradigm were established for the Р68 component. After TAAR1 agonist administration the P68 amplitude in response both to standard and deviant stimuli was increased. These results suggest that the MMN-like response in mice may be modulated through TAAR1-dependent processes (possibly acting through the direct or indirect NMDA modulation), indicating the TAAR1 agonists potential antipsychotic and pro-cognitive activity.

KW - Event-related potentials

KW - Mismatch negativity

KW - Oddball paradigm

KW - RO5263397

KW - Schizophrenia biomarkers

KW - TAAR1

KW - Trace amine-associated receptors

KW - mismatch negativity

KW - FOCUSED ATTENTION

KW - HALOPERIDOL

KW - schizophrenia biomarkers

KW - SCHIZOPHRENIA

KW - trace amine-associated receptors

KW - MMN

KW - TRYPTOPHAN DEPLETION

KW - EVENT-RELATED POTENTIALS

KW - AUDITORY-EVOKED-POTENTIALS

KW - SELECTIVE-ATTENTION

KW - event-related potentials

KW - CENTRAL SEROTONERGIC NEUROTRANSMISSION

KW - oddball paradigm

KW - INVOLUNTARY ATTENTION

UR - http://www.scopus.com/inward/record.url?scp=85068871657&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/trace-amineassociated-receptor-1-agonist-modulates-mismatch-negativitylike-responses-mice

U2 - 10.3389/fphar.2019.00470

DO - 10.3389/fphar.2019.00470

M3 - Article

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - MAY

M1 - 470

ER -