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



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.



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.



Different antidepressants have distinct effects in middle-aged female mice.
Lundbeck Research USA, Paramus, New Jersey (Drs Li and Sanchez); Behavioral Core Facility, Neuroscience Dept., Albert Einstein College of Medicine (Dr Gulinello).
Yan
Y
Li
Lundbeck Research USA, Paramus, New Jersey (Drs Li and Sanchez); Behavioral Core Facility, Neuroscience Dept., Albert Einstein College of Medicine (Dr Gulinello).
Connie
C
Sanchez
Lundbeck Research USA, Paramus, New Jersey (Drs Li and Sanchez); Behavioral Core Facility, Neuroscience Dept., Albert Einstein College of Medicine (Dr Gulinello).
Maria
M
Gulinello
D000375:Aging / Q000187:drug effects* / Q000523:psychology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D003863:Depression / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011897:Random Allocation; D013028:Space Perception / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology; D000069503:Vilazodone Hydrochloride / Q000494:pharmacology; D014796:Visual Perception / Q000187:drug effects; D000078784:Vortioxetine
D000928:Antidepressive Agents; D010879:Piperazines; D011619:Psychotropic Drugs; D013440:Sulfides; D005473:Fluoxetine; D000078784:Vortioxetine; D000068736:Duloxetine Hydrochloride; D000069503:Vilazodone Hydrochloride
SNRI; SSRI; forced swim test; memory tests; multi-modal antidepressant