Alterations in brain microstructure in rats that develop abnormal aggression following peripubertal stress

TY - JOUR

T1 - Alterations in brain microstructure in rats that develop abnormal aggression following peripubertal stress

AU - Walker, Sophie E

AU - Wood, Tobias C

AU - Cash, Diana

AU - Mesquita, Michel

AU - Williams, Steven C R

AU - Sandi, Carmen

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - Exposure to early adversity is implicated in the development of aggressive behavior later in life in some but not all individuals. The reasons for the variability in response to such experiences are not clear but may relate to pre-existing individual differences that influence its downstream effects. Applying structural magnetic resonance imaging (MRI) to a rat model of abnormal aggression induced by peripubertal stress, we examined whether individual differences in the development of an aggressive phenotype following stress exposure were underpinned by variation in the structure of aggression-associated, cortico-limbic brain regions. We also assessed whether responsiveness of the hypothalamic-pituitary-adrenal axis to stress was associated with neurobehavioral outcome following adversity. A subset of the rats exposed to peripubertal stress developed an aggressive phenotype, while the remaining rats were affected in other behavioral domains, such as increased anxiety-like behaviors and reduced sociability. Peripubertal stress led to changes in tissue microstructure within prefrontal cortex, amygdala and hippocampal formation only in those individuals displaying an aggressive phenotype. Attenuated glucocorticoid response to stress during juvenility predicted the subsequent development of an aggressive phenotype in peripubertal stress-exposed rats. Our study establishes a link between peripubertal stress exposure in rats and structural deviations in brain regions linked to abnormal aggression, and points toward low glucocorticoid responsiveness to stress as a potential underlying mechanism. We additionally highlight the importance of considering individual differences in behavioral response to stress when determining neurobiological correlates. This article is protected by copyright. All rights reserved.

AB - Exposure to early adversity is implicated in the development of aggressive behavior later in life in some but not all individuals. The reasons for the variability in response to such experiences are not clear but may relate to pre-existing individual differences that influence its downstream effects. Applying structural magnetic resonance imaging (MRI) to a rat model of abnormal aggression induced by peripubertal stress, we examined whether individual differences in the development of an aggressive phenotype following stress exposure were underpinned by variation in the structure of aggression-associated, cortico-limbic brain regions. We also assessed whether responsiveness of the hypothalamic-pituitary-adrenal axis to stress was associated with neurobehavioral outcome following adversity. A subset of the rats exposed to peripubertal stress developed an aggressive phenotype, while the remaining rats were affected in other behavioral domains, such as increased anxiety-like behaviors and reduced sociability. Peripubertal stress led to changes in tissue microstructure within prefrontal cortex, amygdala and hippocampal formation only in those individuals displaying an aggressive phenotype. Attenuated glucocorticoid response to stress during juvenility predicted the subsequent development of an aggressive phenotype in peripubertal stress-exposed rats. Our study establishes a link between peripubertal stress exposure in rats and structural deviations in brain regions linked to abnormal aggression, and points toward low glucocorticoid responsiveness to stress as a potential underlying mechanism. We additionally highlight the importance of considering individual differences in behavioral response to stress when determining neurobiological correlates. This article is protected by copyright. All rights reserved.

UR - http://www.scopus.com/inward/record.url?scp=85051101020&partnerID=8YFLogxK

U2 - 10.1111/ejn.14061

DO - 10.1111/ejn.14061

M3 - Article

C2 - 29961949

SN - 0953-816X

VL - 48

SP - 1818

EP - 1832

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

IS - 2

ER -