Infant maternal separation impairs adult cognitive performance in BALB/cJ mice.

Rationale: Early life adversity, such as early abuse or parental loss, is thought to increase risk for developing psychiatric disorders in adulthood including mood and anxiety disorders. Human retrospective studies also suggest that early life adversity predicts poor response to antidepressants in adulthood.

Objectives: We used the infant maternal separation (IMS) paradigm to examine the effects of early adversity on adult emotional behavior, the antidepressant response, and cognitive performance in BALB/cJ mice.

Methods: Mice were subjected to either standard facility rearing (SFR) or 3 h of daily separation from the dam from postnatal days 2-15. During adulthood, SFR and IMS mice received chronic treatment (∼3 weeks) with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (18 mg/kg/day), and were assessed for anxiety- and depression-related behavior in the light/dark test and forced swim tests (FST), respectively. We then evaluated the effects of IMS on cognition in the fear conditioning, novel object recognition, and T-maze spatial learning and reversal learning tasks.

Results: Chronic fluoxetine treatment produced robust antidepressant effects in both SFR and IMS mice in the FST. IMS did not affect the antidepressant response, or emotional behavior in the light/dark test or FST. However, IMS reduced fear conditioning to the tone and context, disrupted novel object recognition in females, and impaired both spatial and reversal learning in males.

Conclusions: Our findings suggest that IMS induces deficits in adult emotional, episodic, and spatial memory and reversal learning, but does not alter adult emotional behavior or the response to chronic SSRI treatment in mice.