Abstract
Disrupted social behavior is a core symptom of multiple psychiatric and neurodevelopmental disorders. Many of these disorders are exacerbated by adverse infant experiences, including maltreatment and abuse, which negatively affect amygdala development. Although a link between impaired social behavior, abnormal amygdala function and depressive-like behavior following early adversity has been demonstrated in humans and animal models, the developmental emergence of maltreatment-related social deficits and associated amygdala neural activity are unknown. We used a naturalistic rodent model of maternal maltreatment during a sensitive period, postnatal days 8–12 (PN8–12), which produces social behavior deficits that precede adolescent depressive-like behavior and amygdala dysfunction, to examine social behavior in infancy, periweaning and adolescence. Neural activity in response to the social behavior test was assessed via c-Fos immunohistochemistry at these ages. A separate group of animals was tested for adult depressive-like behavior in the forced swim test. Maltreatment spared infant (PN16–18) social behavior but disrupted periweaning (PN20–22) and adolescent (PN42–48) social behavior. Maltreated rats exhibited blunted neural activation in the amygdala and other areas implicated in social functioning, including the medial prefrontal cortex and nucleus accumbens, at these ages and increased adult depressive-like behavior. These findings may suggest corticolimbic involvement in the emergence of maltreatment-induced social deficits that are linked to adult depressive-like behavior, thereby highlighting potential targets for therapeutic intervention. Understanding how infant experiences influence social behavior and age-specific expression across development may provide insights into basic neural mechanisms of social behaviors and disease-relevant social dysfunction exacerbated by early-life stress.
Highlights
Social behavior deficits are a hallmark feature of psychiatric and neurodevelopmental disorders, including depression, anxiety, autism and schizophrenia,[1,2,3,4] and are associated with abnormal amygdala structure and function.[5,6,7,8] Animal models suggest a causal link between social deficits and the amygdala.[9]
We used a rodent model of maternal maltreatment that consists of creating a low resource environment for the dam from postnatal (PN) days 8–12, which stresses the mother and increases the frequency of negative maternal behaviors that are painful to the pups, pups maintain normal weight gain.[34,49]
Infant rats reared with an maltreating mother exhibited social behavior that did not differ from controls, periweaning and adolescent rats exposed to infant maltreatment spent significantly less time in the social chamber than rats reared with a normal mother (F(1,31) = 9.996, Po0.05; Figure 1a), which is thought to reflect social avoidance.[68]
Summary
Social behavior deficits are a hallmark feature of psychiatric and neurodevelopmental disorders, including depression, anxiety, autism and schizophrenia,[1,2,3,4] and are associated with abnormal amygdala structure and function.[5,6,7,8] Animal models suggest a causal link between social deficits and the amygdala.[9]. The amygdala has a key role in social behavior,[25] the long-term effects of childhood abuse/maltreatment[17,21,27] and the pathophysiology of depression,[43,44] a common outcome of early-life abuse.[18,20,43,44,45] A link between deficient social behavior, abnormal amygdala function and depressive-like behavior following earlylife adversity has been demonstrated in humans[46,47] and rodent models.[42,46,47,48] Despite these findings, the developmental emergence of social behavior deficits and related neural activity following maltreatment are unknown To this end, we used a rodent model of maternal maltreatment that consists of creating a low resource environment (that is, insufficient bedding for nest building) for the dam from postnatal (PN) days 8–12, which stresses the mother and increases the frequency of negative maternal behaviors that are painful to the pups, pups maintain normal weight gain.[34,49] This model closely reflects clinical literature indicating that abused and/or maltreated. Day 1 consisted of a 15-min pretest swim to habituate the rats to the test situation, thereby providing a stable, high level of immobility during the 5-min test on the following day (day 2).[62,70] Two parameters of depressive-like behavior were recorded and scored blindly: time spent immobile, defined as passive floating without struggling, slightly hunched but upright position with minor movements to maintain head above water,[42,48,70] as well as the latency to immobility—the first time at which
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
