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Front Behav Neurosci. 2014 Apr 1;8:109. doi: 10.3389/fnbeh.2014.00109. eCollection 2014.

Learned helplessness and social avoidance in the Wistar-Kyoto rat.

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Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA ; Cell, Molecular, and Developmental Biology, Graduate Biomedical Sciences Program, University of Alabama at Birmingham Birmingham, AL, USA.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.


The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague-Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression.


Wistar-Kyoto (WKY); adrenal; elevated plus maze; forced swim test; heart; maternal separation; social interaction; spontaneously hypertensive rat (SHR)

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