Gottschalk MG, et al. - This study was coordinated to assess the behavioural and molecular effects of a selective serotonin re-uptake inhibitor (SSRI, fluoxetine) and an acetylcholinesterase inhibitor (AChEI, donepezil) on emotional-cognitive endophenotypes of depression and the hippocampal proteome. The researchers concluded that defeat-induced anhedonia and cognitive deficits were ameliorated by fluoxetine (FLX) treatment. Protein interaction network underscored systemic processes of drug mechanisms. FLX reversed functional key pathway changes in the identified social defeat (SD) proteome signature. Promotion of hippocampal AMPA and Ca2+ signaling could underlie FLX's effect.