TY - JOUR

T1 - Effect of Chronic Unpredictable Mild Stress on TAAR2 Knockout Mice

AU - Ефимова, Евгения Викторовна

AU - Шемякова, Таисия Сергеевна

AU - Масленникова, Дарья Дмитриевна

AU - Ваганова, Анастасия Николаевна

AU - Маркина, Алиса Александровна

AU - Гайнетдинов, Рауль Радикович

PY - 2025/10/1

Y1 - 2025/10/1

N2 - Abstract: Objective: Trace amine-associated receptor 2 (TAAR2) is a member of the TAAR family, which was long considered to function primarily as an olfactory receptor. However, recent studies have demonstrated that TAAR2 is also expressed in the brain and may play a role in regulating monoamine systems and behavior. Previous research has shown that TAAR2 knockout (TAAR2-KO) mice exhibit decreased immobilization in the forced swim test, which may indicate reduced depression-like behavior, increased level of dopamine in striatum and increased adult neurogenesis. In the present study, we first investigated expression levels of mRNA of proteins, known to increase in chronic stress in TAAR2-KO mice. Also we studied the effects of chronic unpredictable mild stress (CUMS), a widely used model of depression, on TAAR2-KO mice. Methods: Expression levels of mRNA were assessed using qPCR. Also, to study effects of CUMS TAAR2-KO and wild-type (WT) mice were exposed to mild stressors for four weeks. After four weeks of stress exposure, we assessed basal body temperature and behavior in comparison with intact (unstressed) knockout and wild-type mice. Results and Discussion: Following four weeks of CUMS, neither TAAR2-KO nor WT mice showed significant changes in locomotor activity in the open field test. Stressed animals, both WT and TAAR2-KO exhibited increased grooming frequency. Although increased grooming can be indicative of heightened anxiety, performance in the elevated plus maze showed no differences in time spent in the open arms between groups. In a forced swimming test TAAR2-KO mice shown to be more susceptible to stress, with increased immobilization time. Chronic mild stress is known to affect not only behavior but also body temperature, as prolonged stress exposure can lead to hyperthermia. In our study, stressed animals exhibited increased body temperature. However, while the increase was statistically significant in WT mice, it was much less pronounced in TAAR2-KO mice. Conclusions: Taken together, our findings suggest that, despite previous reports of reduced depression-like behavior in TAAR2-KO mice, the absence of TAAR2 has only a minor effect on the physiological and behavioral responses to chronic unpredictable mild stress.

AB - Abstract: Objective: Trace amine-associated receptor 2 (TAAR2) is a member of the TAAR family, which was long considered to function primarily as an olfactory receptor. However, recent studies have demonstrated that TAAR2 is also expressed in the brain and may play a role in regulating monoamine systems and behavior. Previous research has shown that TAAR2 knockout (TAAR2-KO) mice exhibit decreased immobilization in the forced swim test, which may indicate reduced depression-like behavior, increased level of dopamine in striatum and increased adult neurogenesis. In the present study, we first investigated expression levels of mRNA of proteins, known to increase in chronic stress in TAAR2-KO mice. Also we studied the effects of chronic unpredictable mild stress (CUMS), a widely used model of depression, on TAAR2-KO mice. Methods: Expression levels of mRNA were assessed using qPCR. Also, to study effects of CUMS TAAR2-KO and wild-type (WT) mice were exposed to mild stressors for four weeks. After four weeks of stress exposure, we assessed basal body temperature and behavior in comparison with intact (unstressed) knockout and wild-type mice. Results and Discussion: Following four weeks of CUMS, neither TAAR2-KO nor WT mice showed significant changes in locomotor activity in the open field test. Stressed animals, both WT and TAAR2-KO exhibited increased grooming frequency. Although increased grooming can be indicative of heightened anxiety, performance in the elevated plus maze showed no differences in time spent in the open arms between groups. In a forced swimming test TAAR2-KO mice shown to be more susceptible to stress, with increased immobilization time. Chronic mild stress is known to affect not only behavior but also body temperature, as prolonged stress exposure can lead to hyperthermia. In our study, stressed animals exhibited increased body temperature. However, while the increase was statistically significant in WT mice, it was much less pronounced in TAAR2-KO mice. Conclusions: Taken together, our findings suggest that, despite previous reports of reduced depression-like behavior in TAAR2-KO mice, the absence of TAAR2 has only a minor effect on the physiological and behavioral responses to chronic unpredictable mild stress.

KW - chronic unpredictable mild stress

KW - knockout mice

KW - trace amine-associated receptor 2

KW - trace amines

UR - https://www.mendeley.com/catalogue/ab884a49-1ae1-39e9-9785-9664baf9aac3/

U2 - 10.1134/S1990519X25600279

DO - 10.1134/S1990519X25600279

M3 - Article

VL - 19

SP - 431

EP - 440

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 5

ER -