As with ketamine, classical medications indicated for MDD administered alone or in combination with DA/5-HT modulators (i.e., aripiprazole, cariprazine) either increased above basal level or normalized dampened DA neurons firing/bursts/population activity, only following repeated but not acute regimens (Chernoloz et al., 2009; El Mansari et al., 2020). This evidence concerns the gene HTR5A and major depressive disorder.