# Exploring Consequences of Predator Stress on Behaviors of Mice Lacking Trace Amine-Associated Receptor 5 (TAAR5)

## TL;DR

Mice lacking the TAAR5 receptor show altered dopamine levels and stress responses, suggesting TAAR5 could be a target for treating stress-related disorders.

## Contribution

The study reveals novel insights into how TAAR5 deletion affects dopamine dynamics and behavioral responses to stress in mice.

## Key findings

- TAAR5-KO mice show enhanced dopamine release and reduced anxiety.
- TAAR5-KO mice exhibit active coping during predator stress but increased post-stress anxiety.
- TAAR5 deletion alters recovery from stress and affects object recognition behavior.

## Abstract

What are the main findings?
In mice lacking TAAR5, enhanced accumbal DA release, reduced anxiety, and an increased hedonic state were demonstrated.TAAR5-KO mice were active in coping with predator exposure but were vulnerable to the short-term stress consequences, showing robust anxiety and lowered exploration.

In mice lacking TAAR5, enhanced accumbal DA release, reduced anxiety, and an increased hedonic state were demonstrated.

TAAR5-KO mice were active in coping with predator exposure but were vulnerable to the short-term stress consequences, showing robust anxiety and lowered exploration.

What are the implications of the main finding
Observed behavioral distortions due to TAAR5 deletion imply further pharmacological exploration into the receptor as a drug target for reward deficits, anhedonia, and stress.A robust increase in post-stress anxiety of TAAR5-deficient mice suggests alteration of recovery from stress by potential receptor antagonists.

Observed behavioral distortions due to TAAR5 deletion imply further pharmacological exploration into the receptor as a drug target for reward deficits, anhedonia, and stress.

A robust increase in post-stress anxiety of TAAR5-deficient mice suggests alteration of recovery from stress by potential receptor antagonists.

Recent studies indicated a connection between trace amine-associated receptor 5 (TAAR5) and emotional behaviors related to anxiety and depression; however, the neurobiological basis of this link is still unclear. Using mutant TAAR5 knockout (TAAR5-KO) mice, we explored the consequences of receptor deletion on dopamine (DA) dynamics in the ventral striatum and stress-related behaviors. Voltammetric measurements of DA in the nucleus accumbens (NAc) coupled with electrical stimulation of the ventral tegmental area (VTA) revealed that mice lacking TAAR5 display a greater DA release, while its reuptake is not affected. Behaviorally, mutants were significantly less anxious in the elevated plus maze (EPM) and consumed more sucrose in comparison with wild-type (WT) controls. The new object recognition test (NOR) did not uncover a difference between these genotypes. During predator (rat) stress exposure, mutant and WT mice showed quite distinct responses versus the behavior observed in stressless conditions. Control animals demonstrated a substantial increase in “freezing” (a sign of passive coping), while “running” and “exploring” patterns (signs of active coping) were significantly extended in mice lacking TAAR5. Short-term consequences of stress were explored 24 h following the predator exposure. The absence of TAAR5 did not prevent or reduce stress-induced anxiety in the EPM. In fact, the level of anxiety in mutants reached that observed in control mice. Furthermore, activity in NOR was significantly decreased in mice lacking TAAR5 but not in WT animals. On the other hand, predator exposure resulted in impaired NOR in the WT control, whereas mutants’ performance was not altered. These findings indicate that TAAR5 deletion leads to significant DA imbalance, which might at least partly explain the better stress-coping strategy and other stress-induced behavioral consequences observed in mutant animals.