Distinct Antidepressant-Like and Cognitive Effects of Antidepressants with Different Mechanisms of Action in Middle-Aged Female Mice

BACKGROUND: Cognitive dysfunction is among the key symptoms of major depressive disorder and can be affected by antidepressants. Cognitive decline also occurs in normal aging. The effects of different antidepressants on affective and cognitive domains in older subjects are seldom assessed simultaneously. METHODS: Healthy middle-aged female mice received vehicle or antidepressant (vortioxetine, vilazodone, duloxetine, or fluoxetine) at therapeutic doses. After 1 month treatment, mice were accessed for visuospatial memory and depression-like behavior. A separate cohort of mice received 3 months of treatment and was test for recognition memory and depression-like behavior. RESULTS: After 1 month treatment, vortioxetine improved visuospatial memory and reduced depression-like behavior. Vilazodone reduced depression-like behavior. Duloxetine and fluoxetine were ineffective in both tests. After 3 months treatment, vortioxetine reduced depression-like behavior without affecting recognition memory, while fluoxetine impaired recognition memory. Duloxetine and vilazodone had no effect in both tests. CONCLUSION: Different antidepressants have distinct effects in middle-aged female mice.