The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice.

Rationale: Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that has a particular role in regulating dopaminergic, serotonergic, and glutamatergic transmission. TAAR1 agonists have shown pro-cognitive activities. However, it remains largely unknown of the effects of TAAR1 agonists on memory performance.

Objectives: Here, by using the mice novel object recognition (NOR) test, we examined the effects of the selective TAAR1 partial agonist RO5263397 on recognition memory.

Results: We found that RO5263397 significantly enhanced the retrieval of short-term memory (STM; 20 min after training) both in male and female mice. RO5263397 promoted the retrieval of STM in the wild-type (WT) littermates but not TAAR1-KO mice, indicating that the effects of RO5263397 were dependent on TAAR1. Interestingly, compared to their WT litters, TAAR1-KO mice showed similar levels of STM, suggesting that genetic deletion of taar1 gene did not affect the STM retrieval. Furthermore, RO5263397 also promoted the retrieval of long-term NOR memory (24 h after training).

Conclusions: These results indicate that TAAR1 activation promotes NOR memory retrieval. Consistent with previous studies, our finding further suggests that TAAR1 agonists have pro-cognitive properties.