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Infant Maternal Separation Impairs Adult Cognitive Performance in BALB/cJ Mice

Overview
Specialty Pharmacology
Date 2011 Feb 19
PMID 21331521
Citations 30
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Abstract

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.

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References
1.
Phillips R, LeDoux J . Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci. 1992; 106(2):274-85. DOI: 10.1037//0735-7044.106.2.274. View

2.
Aisa B, Tordera R, Lasheras B, Del Rio J, Ramirez M . Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats. Psychoneuroendocrinology. 2007; 32(3):256-66. DOI: 10.1016/j.psyneuen.2006.12.013. View

3.
Navailles S, Zimnisky R, Schmauss C . Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress. Dev Neurosci. 2010; 32(2):139-48. PMC: 2919512. DOI: 10.1159/000293989. View

4.
Anisman H, Zaharia M, Meaney M, Merali Z . Do early-life events permanently alter behavioral and hormonal responses to stressors?. Int J Dev Neurosci. 1998; 16(3-4):149-64. DOI: 10.1016/s0736-5748(98)00025-2. View

5.
Macqueen G, Ramakrishnan K, Ratnasingan R, Chen B, Young L . Desipramine treatment reduces the long-term behavioural and neurochemical sequelae of early-life maternal separation. Int J Neuropsychopharmacol. 2003; 6(4):391-6. DOI: 10.1017/S1461145703003729. View