Moreover, preclinical evidence has shown that ketamine displays other mechanisms of action that may provide insights into shared mechanisms between migraine and MDD involving actions at 5HT1B receptors and 5HT transporters, increasing 5HT, GABAA, and nicotinic acetylcholine, and increasing expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, specifically, the HCN1 receptors [121–123]. Here, SLC6A4 is linked to major depressive disorder.