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Recently proposed theories implicate signaling pathways related to synaptic plasticity as critical to the molecular mechanisms of antidepressants, with particular focus on the ERK pathway regarding emotional responses (Malberg et al. Chronic stress increases depressive-like behaviors and decreases ERK2 in the hippocampus, an effect alleviated in part by treatment with fluoxetine (Qi et al. Furthermore, chronic administration of lithium or valproate, mood stabilizers used in the treatment of manic depression, stimulates the MAPK pathway in the rat hippocampus (Einat et al, . In our previous work, we have shown that mRNA and protein expression of ERK2, specifically within the hippocampus, is testosterone dependent (Carrier and Kabbaj, 2012d). GNX adult male rats had reduced ERK2 expression throughout the hippocampal formation, compared to sham-operated controls. 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