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

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.