Maternal separation increases later immobility during forced swim in guinea pig pups: evidence for sensitization of a depressive‐like state

Dong

Intl J of Devlp Neuroscience

et al. 2017

There is little research on the effects of adolescent administration of antidepressants on behavioural function and inflammation in early-life stressed adult mice. Using maternal separation (MS), a paradigm of early adversity, we investigated the effects of adolescent (PND 33-54) escitalopram (ES; 10mg/kg) exposure on depression- and anxiety-like behaviours and the levels of inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor [TNF]-α, and IL-10) in the ventral hippocampus (HPV), prefrontal cortex (PFC), and serum in adult (PND 61) male offspring mice. The results showed that MS has no effect on locomotor activity, but increased depression-like behaviours in the saccharin preference test and increased anxiety-like behaviours in the social preference and elevated plus maze tests. MS increased the levels of IL-1β in the HPV, PFC, and serum, while decreasing the level of IL-10 in the HPV. Furthermore, adolescent ES treatment inhibited these depression- and anxiety-like behaviours, decreased the levels of IL-1β, and increased the level of IL-10 in the HPV. The results also showed that there are no effects of chronic escitalopram administration on normal behaviour in control mice. Taken together, the current data provide experimental evidence that MS increases depression and anxiety levels in adult male offspring. Additionally, the findings support the idea that early pharmacological intervention with ES may be an effective treatment for reducing the behavioral abnormalities induced by early adversity and regulating the underlying inflammatory mechanisms involved.

Section: Discussionmentioning

confidence: 99%

Adolescent escitalopram prevents the effects of maternal separation on depression‐ and anxiety‐like behaviours and regulates the levels of inflammatory cytokines in adult male mice

Dong

Intl J of Devlp Neuroscience

et al. 2017

“…Together, these findings indicate that a several-hour period of separation of guinea pig pups from the attachment figure in a threatening (i.e., novel, brightly lit) environment evokes an inflammatory-mediated depressive-like response that sensitizes with repeated separation. The validity of this model for the study of depression is supported by the recent finding that an initial 3-hour separation also increased later depressive-like responding in the most widely used screen for antidepressant medication, i.e., previous separation increased immobility in the forced swim test (Hennessy et al, 2017).…”

Section: Introductionmentioning

confidence: 86%

Central neuroimmune activity and depressive-like behavior in response to repeated maternal separation and injection of LPS

Hennessy

Deak

Sensenbaugh

et al. 2019

Physiology & Behavior

Self Cite

Disruption of attachment relations in early life is linked to greater vulnerability to depressive illness at later ages. Evidence suggests this process involves stress-induced activation of central inflammatory factors, though the specific mediators and processes involved are not known. We used a guinea pig model in which effects of maternal separation appear more clearly due to absence of the attachment figure than is the case for other laboratory rodents. Separation in a novel environment on two consecutive days evoked a depressive-like behavioral response that sensitized during a final test 9 days later. At this time, prior separation blunted the response of prostaglandin synthesizing enzymes (COX-2 and mPGES) and chemokines (CXCL-1 and MCP-1) 120 min following injection with lipopolysaccharide and isolation in a novel cage. The blunted response was not associated with a greater plasma cortisol elevation. In addition, injection of saline just prior to isolation at the oldest age elicited small, but significant, elevations in several signaling molecules, particularly at 30 min. These results demonstrate lasting central inflammatory consequences of our separation procedure. However, contrary to expectations, sensitization of depressive-like behavior was not associated with an increase in expression of neuroimmune mediators to inflammatory challenge. Together with earlier findings, the results suggest a multistep process in which inflammatory response to an initial separation affects downstream mediators to sensitize depressive-like behavior.

“…Maternal separation (MS) in rodents, especially rats, has been widely used to elicit the effect of early life stress on mood disorders (Tractenberg et al, 2016;Vetulani, 2013). MS has been reported to increase anxiety and depressive behaviors and cause cognitive disorder in adulthood, which was accomplished by alterations in HPA axis, decreased BDNF expression and altered structural and functional plasticity in the medial prefrontal cortex and hippocampus in rats and mice (Hennessy, Schreibeis, Schiml, & Deak, 2017;Musazzi et al, 2009;Seo et al, 2017;Tractenberg et al, 2016;Vetulani, 2013; van Zyl, . Though most mental disorders in humans often begin to onset during adolescence (Kessler et al, 2007), previous studies in rodent models, however, mostly focused on the adult outcomes of early life stress (Schroeder, Notaras, Du, & Hill, 2018).…”

mentioning

confidence: 99%

Effect of early life stress on anxiety and depressive behaviors in adolescent mice

Chen

et al. 2020

Brain and Behavior

Introduction Adolescence is a critical period for physical and mental development. The effect of early life stress on mood disorders has been intensively studied in adults using rodent models, but it has been less studied in adolescents. The present study aimed to examine the effect of early life stress on anxiety‐related and depression‐like behaviors in adolescent C57BL/6 mice and the sex difference. Methods C57BL/6 mice of both sexes were used, and early life stressors included maternal separation (MS, P2‐12, 4 hr per day), restraint stress (RS, P33 to 39, 4 hr per day), and their combination (MRS). Open field test, elevated plus maze, and forced swimming test were performed at different time points during adolescence and adulthood. Results It was found that MS did not affect the anxiety‐related behaviors of both males and females tested on P30‐31 and P41‐42. RS decreased the anxiety level in adolescent males but did not affect it in the females. MS, RS, and MRS all significantly increased the depression‐like behavior in adolescent males, but only MRS increased the depression‐like behavior in adolescent females. All effects on adolescent males and females did not persist into adulthood. Conclusion The present results showed that early life stress affected anxiety‐related and depression‐like behavior in adolescent mice in manners depending on the nature of stress, the developmental period, and sex.