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Heterogeneous Stock Rats: A Model To Study The Genetics Of Despair And Fluoxetine Resistance in Adolescence
Author(s) -
Woods Leah C Solberg,
Holl Katie,
He Hong,
Wedemeyer Michael,
Clopton Larissa,
Wert Stephanie,
Meckes Jeanie,
Kastner Abigail,
Palmer Abraham,
Redei Eva
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1058.10
Subject(s) - fluoxetine , behavioural despair test , antidepressant , endocrinology , genetic model , medicine , major depressive disorder , animal models of depression , psychology , gene , biology , genetics , hippocampus , serotonin , receptor , amygdala
Major depressive disorder is a complex illness caused by both genetics and the environment. Antidepressant resistance also has a genetic component. To date, very few genetic variations have been identified for major depression or antidepressant resistance. In the current 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 WKY rat, one of the founders of the HS colony, is a known animal model of depression, in both adults and adolescents, and has been found to be resistant to fluoxetine anti‐depressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair behavior and response to fluoxetine treatment. We assessed despair behavior using a modified Forced Swim Test (FST) in four‐week old male and female HS rats. A separate group of rats were given sub‐acute treatment with either saline or fluoxetine prior to the FST and immobility, climbing and swimming behaviors were scored. Finally, we tested whether or not blood transcript levels previously identified to be differentially expressed in depressed human and rat models correlate with despair behavior in the HS rats. We demonstrate that 4‐week old HS rats have large variation in despair behavior in the FST and that most HS rats are resistant to treatment with fluoxetine. We also demonstrate that four genes previously identified as differentially expressed in the blood of depressed rats and humans are also negatively correlated with despair behavior in the HS rats. Taken together, these data demonstrate that the HS rat is a suitable model for investigating the underlying genetic basis of despair behavior as well as resistance to fluoxetine and that these studies will likely translate to depression in humans. Support or Funding Information P50 DA037844, Davee Foundation