Although, we could not rule out the possibility of exogenous SPX1 expression in the dHb SPX1-negative neurons, which is caused by the Tg(gpr151:gal4vp16) driver line, our results are consistent with the earlier observation that the administration of an SPX-based GALR2-specific agonist induces anti-depressive and anxiolytic effects in mice (Reyes-Alcaraz et al., 2016; Yun et al., 2019), and that Galr2/3 knockout mice expressed an anxiety and depression-like phenotype (Bailey et al., 2007; Lu et al., 2008; Brunner et al., 2014). This evidence concerns the gene HELB and major depressive disorder.