In lithium-pilocarpine-induced epileptic rats, depression-like behaviors correlated with an upregulation of presynaptic 5-HT1A receptors in the raphe nucleus compromised raphe-hippocampal 5-HT transmission, and caused the subsequent downregulation of the postsynaptic 5-HT1A in the hippocampus [115]. This evidence concerns the gene HTR1A and major depressive disorder.