Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats

Rosemarie E. Perry, Millie Rincón-Cortés, Stephen H. Braren, Annie N. Brandes-Aitken, Maya Opendak, Gabriella Pollonini, Divija Chopra, C. Cybele Raver, Cristina M. Alberini, Clancy Blair, Regina M. Sullivan

Research output: Contribution to journalArticle

Abstract

It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can “get under the skin” to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of “scarcity-adversity,” which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology. Results showed that early-life scarcity-adversity exposure increased social avoidance when offspring were tested in a social approach test in peri-adolescence. Furthermore, early-life scarcity-adversity led to blunted hypothalamic-pituitary-adrenal (HPA) axis activity as measured via adrenocorticotropic hormone (ACTH) and corticosterone (CORT) reactivity following the social approach test. Western blot analysis of brain tissue revealed that glucocorticoid receptor levels in the dorsal (but not ventral) hippocampus and medial prefrontal cortex were significantly elevated in scarcity-adversity reared rats following the social approach test. Finally, pharmacological repletion of CORT in scarcity-adversity reared peri-adolescents rescued social behavior. Our findings provide causal support that early-life scarcity-adversity exposure negatively impacts social development via a hypocorticosteronism-dependent mechanism, which can be targeted via CORT administration to rescue social behavior.

Original languageEnglish (US)
Article number100716
JournalDevelopmental Cognitive Neuroscience
Volume40
DOIs
StatePublished - Dec 2019

Fingerprint

Social Behavior
Corticosterone
Phenotype
Glucocorticoid Receptors
Poverty
Prefrontal Cortex
Adrenocorticotropic Hormone
Rodentia
Hippocampus
Western Blotting
Pharmacology
Brain
Research

Keywords

  • CORT
  • Corticosterone
  • Cortisol
  • Development
  • Early-life adversity
  • Glucocorticoid
  • Hippocampus
  • HPA axis
  • Hypocorticosteronism
  • Hypocortisolism
  • Poverty
  • Prefrontal cortex
  • Scarcity
  • Social avoidance
  • Social behavior
  • Stress

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

Perry, R. E., Rincón-Cortés, M., Braren, S. H., Brandes-Aitken, A. N., Opendak, M., Pollonini, G., ... Sullivan, R. M. (2019). Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats. Developmental Cognitive Neuroscience, 40, [100716]. https://doi.org/10.1016/j.dcn.2019.100716

Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats. / Perry, Rosemarie E.; Rincón-Cortés, Millie; Braren, Stephen H.; Brandes-Aitken, Annie N.; Opendak, Maya; Pollonini, Gabriella; Chopra, Divija; Raver, C. Cybele; Alberini, Cristina M.; Blair, Clancy; Sullivan, Regina M.

In: Developmental Cognitive Neuroscience, Vol. 40, 100716, 12.2019.

Research output: Contribution to journalArticle

Perry, Rosemarie E. ; Rincón-Cortés, Millie ; Braren, Stephen H. ; Brandes-Aitken, Annie N. ; Opendak, Maya ; Pollonini, Gabriella ; Chopra, Divija ; Raver, C. Cybele ; Alberini, Cristina M. ; Blair, Clancy ; Sullivan, Regina M. / Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats. In: Developmental Cognitive Neuroscience. 2019 ; Vol. 40.
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abstract = "It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can “get under the skin” to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of “scarcity-adversity,” which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology. Results showed that early-life scarcity-adversity exposure increased social avoidance when offspring were tested in a social approach test in peri-adolescence. Furthermore, early-life scarcity-adversity led to blunted hypothalamic-pituitary-adrenal (HPA) axis activity as measured via adrenocorticotropic hormone (ACTH) and corticosterone (CORT) reactivity following the social approach test. Western blot analysis of brain tissue revealed that glucocorticoid receptor levels in the dorsal (but not ventral) hippocampus and medial prefrontal cortex were significantly elevated in scarcity-adversity reared rats following the social approach test. Finally, pharmacological repletion of CORT in scarcity-adversity reared peri-adolescents rescued social behavior. Our findings provide causal support that early-life scarcity-adversity exposure negatively impacts social development via a hypocorticosteronism-dependent mechanism, which can be targeted via CORT administration to rescue social behavior.",
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AU - Braren, Stephen H.

AU - Brandes-Aitken, Annie N.

AU - Opendak, Maya

AU - Pollonini, Gabriella

AU - Chopra, Divija

AU - Raver, C. Cybele

AU - Alberini, Cristina M.

AU - Blair, Clancy

AU - Sullivan, Regina M.

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