TMEM97 and Anxiety: However, previous studies using pharmacological agents found that modulation of s2R reduced anxiety-/depressive-like behaviors in naive rodents through a mechanism interpreted as agonism (Sánchez et al., 1997; Sánchez and Papp, 2000), which seemingly conflicts with our finding since Tmem97 KO mice could be interpreted as equivalent to “antagonistic” modulation of the receptor.