TY - JOUR

T1 - Enhanced Aggression, Reduced Self-Grooming Behavior and Altered 5-HT Regulation in the Frontal Cortex in Mice Lacking Trace-Amine Associated Receptor 1 (TAAR1)

AU - Жуков, Илья Сергеевич

AU - Карпова, Инесса

AU - Кротова, Наталья Алексеевна

AU - Тиссен, Илья Юрьевич

AU - Демин, Константин Андреевич

AU - Шабанов, Петр Дмитриевич

AU - Будыгин, Евгений Александрович

AU - Калуев, Алан Валерьевич

AU - Гайнетдинов, Рауль Радикович

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/11/15

Y1 - 2022/11/15

N2 - The Trace Amine-Associated Receptor 1 (TAAR1) is one of the six functional receptors belonging to the family of monoamine-related G protein-coupled receptors (TAAR1-TAAR9) found in humans. However, the exact biological mechanisms of TAAR1 central and peripheral action remain to be fully understood. TAAR1 is widely expressed in the prefrontal cortex and several limbic regions, interplaying with the dopamine system to modulate the reward circuitry. Recent clinical trials suggest the efficacy of TAAR1 agonists as potential novel antipsychotic agents. Here, we characterize behavioral and neurochemical phenotypes of TAAR1 knockout mice, focusing on aggression and self-grooming behavior that both strongly depend on the monoaminergic signaling and cortico-striatal and cortico-limbic circuits. Overall, we report increased aggression in these knockout mice in the resident-intruder test, accompanied by reduced self-grooming behavior in the novelty-induced grooming test, and by higher cortical serotonin (5-HT) tissue levels. Further studies are necessary to explore whether TAAR1-based therapies can become potential novel treatments for a wide range of neuropsychiatric disorders associated with aggression.

AB - The Trace Amine-Associated Receptor 1 (TAAR1) is one of the six functional receptors belonging to the family of monoamine-related G protein-coupled receptors (TAAR1-TAAR9) found in humans. However, the exact biological mechanisms of TAAR1 central and peripheral action remain to be fully understood. TAAR1 is widely expressed in the prefrontal cortex and several limbic regions, interplaying with the dopamine system to modulate the reward circuitry. Recent clinical trials suggest the efficacy of TAAR1 agonists as potential novel antipsychotic agents. Here, we characterize behavioral and neurochemical phenotypes of TAAR1 knockout mice, focusing on aggression and self-grooming behavior that both strongly depend on the monoaminergic signaling and cortico-striatal and cortico-limbic circuits. Overall, we report increased aggression in these knockout mice in the resident-intruder test, accompanied by reduced self-grooming behavior in the novelty-induced grooming test, and by higher cortical serotonin (5-HT) tissue levels. Further studies are necessary to explore whether TAAR1-based therapies can become potential novel treatments for a wide range of neuropsychiatric disorders associated with aggression.

KW - TAAR1

KW - aggression

KW - dopamine

KW - frontal cortex

KW - gene knockout

KW - grooming

KW - resident-intruder

KW - serotonin

UR - http://www.scopus.com/inward/record.url?scp=85142626364&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/3bb52de3-5aff-3a6b-87d2-6f217a024f74/

U2 - 10.3390/ijms232214066

DO - 10.3390/ijms232214066

M3 - Article

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 22

M1 - 14066

ER -