HTR1A and Anxiety: While their direct role in anxiety onset is unclear, the contribution of the serotonergic system is evident as 5-HT1A receptor knockout mice exhibit increased anxiety-like behavior in assays such as the elevated-plus maze and open-field test, both of which provide face and predictive validity in human models of anxiety (Hirshfeld et al., 1992; Graeff et al., 1998; Lesch, 2005).