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Adolescent Corticosterone and TrkB Pharmaco-Manipulations Sex-Dependently Impact Instrumental Reversal Learning Later in Life

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Last modified
  • 03/05/2025
Type of Material
Authors
    Elizabeth T. Barfield, Emory UniversityShannon L Gourley, Emory University
Language
  • English
Date
  • 2017-12-07
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2017 Barfield and Gourley.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1662-5153
Volume
  • 11
Grant/Funding Information
  • The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD011132.
  • This work was supported by an National Institutes of Health (NIH) BRAINS award (MH101477) and the National Science Foundation Graduate Research Fellowship Program under grant number DGE-1444932.
Abstract
  • Early-life trauma can increase the risk for, and severity of, several psychiatric illnesses. These include drug use disorders, and some correlations appear to be stronger in women. Understanding the long-term consequences of developmental stressor or stress hormone exposure and possible sex differences is critically important. So-called “reversal learning” tasks are commonly used in rodents to model cognitive deficits in stress- and addiction-related illnesses in humans. Here, we exposed mice to the primary stress hormone corticosterone (CORT) during early adolescence (postnatal days 31–42), then tested behavioral flexibility in adulthood using an instrumental reversal learning task. CORT-exposed female, but not male, mice developed perseverative errors. Despite resilience to subchronic CORT exposure, males developed reversal performance impairments following exposure to physical stressors. Administration of a putative tyrosine kinase receptor B (trkB) agonist, 7,8-dihydroxyflavone (7,8-DHF), during adolescence blocked CORT-induced errors in females and improved performance in males. Conversely, blockade of trkB by ANA-12 impaired performance. These data suggest that trkB-based interventions could have certain protective benefits in the context of early-life stressor exposure. We consider the implications of our findings in an extended “Discussion” section.
Author Notes
Keywords
Research Categories
  • Psychology, Behavioral
  • Health Sciences, Pharmacology

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