Dataset Information

Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment.

ABSTRACT: Despite the enormous negative impact of excessive aggression for individuals and societies, there is a paucity of treatments. Here, using a peripubertal stress model of heightened aggression in rats, we investigated the involvement of the glucocorticoid system and tested the effectiveness of antiglucocorticoid treatment to normalize behavior. We assessed peripubertal stress-induced changes in glucocorticoid (GR) and mineralocorticoid (MR) gene expression in different amygdala nuclei and hippocampus, and report a specific increase in GR mRNA expression in the central amygdala (CeA). Administration of mifepristone (10?mg/kg), a GR antagonist, before stressor exposure at peripuberty prevented the habituation of plasma corticosterone responses observed throughout the stress protocol. This treatment also prevented the increase in aggression and GR expression in the CeA observed in peripubertally stressed rats at adulthood. Viral downregulation of CeA GR expression at adulthood led to reduced aggression. Subsequently, we showed that a brief, 3-day, treatment with mifepristone at adulthood was effective to normalize the abnormal aggression phenotype in peripubertally stressed rats. Our results support a key role for GR actions during peripubertal stress for the long-term programming of heightened aggression. Strikingly, they also support the translational interest of testing the effectiveness of mifepristone treatment to diminish reactive aggression in early adversity-related human psychopathologies.

SUBMITTER: Papilloud A

PROVIDER: S-EPMC6372583 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment.

Papilloud Aurelie A Veenit Vandana V Tzanoulinou Stamatina S Riccio Orbicia O Zanoletti Olivia O Guillot de Suduiraut Isabelle I Grosse Jocelyn J Sandi Carmen C

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180604 4

Despite the enormous negative impact of excessive aggression for individuals and societies, there is a paucity of treatments. Here, using a peripubertal stress model of heightened aggression in rats, we investigated the involvement of the glucocorticoid system and tested the effectiveness of antiglucocorticoid treatment to normalize behavior. We assessed peripubertal stress-induced changes in glucocorticoid (GR) and mineralocorticoid (MR) gene expression in different amygdala nuclei and hippocam ...[more]

PMID: 29941978

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Project description:BACKGROUND:Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. METHODS:Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat-related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). RESULTS:Even after stringently matching for several potentially confounding variables - including baseline internalizing symptoms, socioeconomic status and IQ - childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post-baseline exposure to major stressful life events and internalizing symptoms at follow-up. We also showed, for the first time, that amygdala reactivity at baseline and also post-baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. CONCLUSIONS:These findings provide support for the view that maltreatment is a potent developmental insult leading to long-lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation).

Dataset Information

Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment.

Publications

Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment.

Similar Datasets

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