Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence

K. Holl, H. He, M. Wedemeyer, L. Clopton, S. Wert, J. K. Meckes, R. Cheng, A. Kastner, A. A. Palmer, E. E. Redei, L. C. Solberg Woods*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Major depressive disorder (MDD) is a complex illness caused by both genetic and environmental factors. Antidepressant resistance also has a genetic component. To date, however, very few genes have been identified for major depression or antidepressant resistance. In this study, we investigated whether outbred heterogeneous stock (HS) rats would be a suitable model to uncover the genetics of depression and its connection to antidepressant resistance. The Wistar Kyoto (WKY) rat, one of the eight founders of the HS, is a recognized animal model of juvenile depression and is resistant to fluoxetine antidepressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair-like behavior and response to fluoxetine treatment. We assessed heritability of despair-like behavior and response to sub-acute fluoxetine using a modified forced swim test (FST) in 4-week-old HS rats. We also tested whether blood transcript levels previously identified as depression biomarkers in adolescent human subjects are differentially expressed in HS rats with high vs. low FST immobility. We demonstrate heritability of despair-like behavior in 4-week-old HS rats and show that many HS rats are resistant to fluoxetine treatment. In addition, blood transcript levels of Amfr, Cdr2 and Kiaa1539, genes previously identified in human adolescents with MDD, are differentially expressed between HS rats with high vs. low immobility. These data demonstrate that FST despair-like behavior will be amenable to genetic fine-mapping in adolescent HS rats. The overlap between human and HS blood biomarkers suggest that these studies may translate to depression in humans.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalGenes, Brain and Behavior
Issue number2
StatePublished - Feb 2018


  • Adolescence
  • QTL mapping
  • RNA expression
  • Wistar Kyoto
  • antidepressant resistance
  • blood transcript levels
  • depression biomarkers
  • forced swim test
  • major depression
  • outbred rats

ASJC Scopus subject areas

  • Neurology
  • Genetics
  • Behavioral Neuroscience


Dive into the research topics of 'Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence'. Together they form a unique fingerprint.

Cite this