“Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear.” Using middle-aged C57BL/6 mice for this study, Li and colleagues compared the effects of the SSRI antidepressant fluoxetine and multimodal antidepressant vortioxetine on cognitive and affective behaviors. Brain stem cell proliferation, growth factor and neuroplasticity-related gene expression were also studied.
Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in the middle-aged mice. Vortioxetine, but not fluoxetine, also increased hippocampal expression of a range of neuroplasticity-related genes. Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. The study concluded that a change in the expression of neuronal plasticity genes by the antidepressant Vortioxetine was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.
Li Y, Abdourahman A, Tamm JA, Pehrson AL, Sánchez C and Gulinello M: Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice. Pharmacol. Biochem. Behav. 135: 70-82 (2015).

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