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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2017.00237

Adolescent corticosterone and trkB pharmaco-manipulations sex-dependently impact instrumental reversal learning later in life

  • 1Yerkes National Primate Research Center, Emory University, United States
  • 2Department of Pediatrics, Emory University, United States
  • 3Graduate Program in Neuroscience, Emory University, United States
  • 4Department of Psychiatry and Behavioral Sciences, Emory University, United States

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-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.

Keywords: juvenile, impulsivity, BDNF, tropomyosin receptor kinase B, dihydroxyflavone

Received: 28 Jul 2017; Accepted: 14 Nov 2017.

Edited by:

Nuno Sousa, Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS), Portugal

Reviewed by:

Alicia Izquierdo, University of California, Los Angeles, United States
Caitlin A. Orsini, University of Florida, United States
Nicholas W. Simon, University of Pittsburgh, United States  

Copyright: © 2017 Barfield and Gourley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Shannon L. Gourley, Emory University, Yerkes National Primate Research Center, NS bldg, 954 Gatewood Rd. NE, Atlanta, 30329, GA, United States,