We have shown previously the blockade of AMPA receptor activity with its antagonist CNQX ameliorates the antidepressant-like effects of reelin treatment and reelin restores long-term potentiation (LTP) in the hippocampus following chronic stress, suggesting regulation of synaptic plasticity is a key mechanism through which reelin administration reverses depression-like behavior (Brymer et al., 2020; Johnston et al., 2023). This evidence concerns the gene RELN and major depressive disorder.