[Abstract Title]. - Society for Neuroscience

NIDA 5P01DA021633-02 (HA & SJW)
Title: Selectively-bred low novelty-seeking rats exhibit exaggerated anxiety- and depression-like
behavior: a novel animal model of depression?
Authors: *A. D. ABRAHAM, S. M. CLINTON, I. A. KERMAN, T. A. BEDROSIAN, S. J.
WATSON, H. AKIL;
Molec Behav Neurosci Inst., Univ. Michigan, Ann Arbor, MI
Abstract: We have selectively bred Sprague-Dawley (SD) rats according to innate differences in
“novelty-seeking”, a trait in rodents that predicts several key facets of emotional reactivity,
including anxiety-like behavior, neuroendocrine stress response, and propensity to selfadminister
drugs of abuse. Our High Responder (HR)-bred rats vigorously explore new
environments compared to Low Responders (LR), which exhibit very little exploration. Notably,
LR rats exhibit exaggerated anxiety- and depressive- like behaviors compared to their HR
counterparts, suggesting that LR-bred rats may represent a novel animal model of depression.
The present experiment directly compared LR-bred rats with an established animal model of
depression - the Wistar-Kyoto (WKY) rat, which is known to exhibit a variety of depressive-like
behavioral and physiological abnormalities. Adult HR- and LR- bred males from the 17 th
generation of our breeding colony as well as WKY and SD rats purchased from Charles River
(N=12 per group) were subjected to a test battery to assess (1) depression-like behavior in the
Forced Swim Test, (2) locomotor response to novelty, and (3) anxiety-like behavior in the Light-
Dark Box and the Elevated Plus Maze. The data demonstrate that LR and WKY rats show
similarly high levels of immobility on the Forced Swim Test, with both groups exhibiting greater
immobility than HRs and purchased SD rats. WKY rats, like LR rats, exhibit very low levels of
novelty-induced locomotor activity. HR rats show very high levels of activity in the novel
environment, with purchased SD rats exhibiting an intermediate level of activity. LR and WKY
rats behave similarly in the anxiety tests, both showing exaggerated anxiety-like behaviors
compared to HR and purchased SD rats. Overall these findings support the notion that LR rats
represent a novel animal model of depression with concurrent anxiety. What distinguishes the
LR “depression model” from other models, such as the WKY rat, is that its depressive phenotype
cannot be attributed to strain differences, but rather, is likely linked to underlying genetic
differences which have been uncovered via selective breeding.
Disclosures: A.D. Abraham , None; S.M. Clinton, None; I.A. Kerman, None; T.A.
Bedrosian, None; S.J. Watson, None; H. Akil, None.
Poster
283. Stress-Regulated Pathways II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm