Early life maternal separation induces sex-specific antidepressant-like responses but has minimal effects on adult stress susceptibility in mice

Abstract

Early life stress is known to increase the risk of depression and anxiety disorders, which are highly prevalent conditions that disproportionately affect women. However, the results of preclinical studies have been mixed, with some work suggesting that early life stress promotes anxiety-like behavior and/or increases susceptibility to subsequent stressors, and other research suggesting that early life stress reduces anxiety-like behavior and/or confers resilience to subsequent stress exposure. It is likely that factors such as sex and the timing and severity of early life and adult stress exposure dictate whether a particular early life experience promotes adaptive vs. maladaptive behavior later in life. Most work in this area has focused exclusively on males, but several sex differences in the effects of early life stress on subsequent stress susceptibility have been reported. The current study examined the impact of early life maternal separation on susceptibility to behavioral alterations induced by 3 days of variable stress in adulthood in male and female c57BL6 mice. Our results indicate that 3 days of adult stress is sufficient to increase anxiety-like behavior in several paradigms and to increase immobility in the forced swim test. In contrast, a history of maternal separation reduces anxiety-like behavior in several tests, particularly in males. These findings could contribute to our understanding of sex differences in mental illness by demonstrating that males are more likely than females to display adaptive responses to mild early life stressors.

Strain-specific changes in nucleus accumbens transcriptome and motivation for food reward in mice exposed to maternal separation

“…Most of previous works conducted in C57Bl/6 exposed to MS report long-term effects on behaviour, only when animals were re-exposed to an additional stressor such as early weaning at PND17 (Tchenio et al, 2017), or chronic social defeat or UCMS at adulthood (Peña et al, 2017(Peña et al, , 2019. Without additional stress, emotional behaviours in MS C57Bl/6 mice generally did not significantly differ from controls (Millstein and Holmes, 2007;Tractenberg et al, 2016;Peña et al, 2017Peña et al, , 2019Baugher and Sachs, 2022;Shin et al, 2023). On the other hand, C3H/HeN strain used in the present study has been previously reported to induce gut dysfunction after MS (Riba et al, 2018;Ilchmann-Diounou et al, 2019;Rincel et al, 2019) and emotional impairments in a multi-hit model combining MS, maternal UCMS and prenatal infection (Rincel et al, 2019).…”

Strain-specific changes in nucleus accumbens transcriptome and motivation for palatable food reward in mice exposed to maternal separation

“…Most of previous works conducted in C57Bl/6J exposed to MS report long-term effects on behavior, only when animals are re-exposed to an additional stressor such as early weaning at PND17 ( 48 ), chronic social defeat or unpredictable chronic mild stress (UCMS) at adulthood ( 25 , 26 ). Without additional stress, emotional behaviors in MS C57Bl/6J mice generally do not significantly differ from controls ( 25–27 , 43 , 49 , 50 ). On the other hand, C3H/HeN strain displays gut dysfunction after MS ( 17 , 30 , 31 ) and emotional impairments in a multi-hit model combining MS, maternal UCMS and prenatal infection ( 31 ).…”

Narrative Review of the Complex Interaction between Pain and Trauma in Children: A Focus on Biological Memory, Preclinical Data, and Epigenetic Processes

“…Factors such as sex and the timing and severity of early-life and adult stress exposure seem to play a key role in determining whether a particular early-life experience would promote adaptive or maladaptive behavior later in life. Thus, researchers are now called to pay attention to individual differences that may impact different risk factors, the type of trauma, and the behavioral measures of symptoms before drawing conclusions [165][166][167][168][169]. These aspects are critical to be able to relate behavioral symptoms with their neural correlates and to establish effective drug development and drug testing platforms.…”