title: Learned helplessness and social avoidance in the Wistar-Kyoto rat.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Clinton
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Nateka L
authors.initials: NL
authors.lastname: Jackson
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Birmingham, AL, USA.
authors.forename: Ilan A
authors.initials: IA
authors.lastname: Kerman
keywords: Wistar-Kyoto (WKY); adrenal; elevated plus maze; forced swim test; heart; maternal separation; social interaction; spontaneously hypertensive rat (SHR)
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