Nam Hyungwoo, Clinton Sarah M, Jackson Nateka L, Kerman Ilan A
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.
Front Behav Neurosci. 2014 Apr 1;8:109. doi: 10.3389/fnbeh.2014.00109. eCollection 2014.
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）大鼠是一种公认的抑郁模型，其特点是在各种测试中焦虑和抑郁样行为增加。在这里，我们进一步描述了WKY大鼠中与抑郁相关的特定行为和功能领域的变化。此外，由于早期生活经历有力地塑造了情绪行为，我们还使用新生鼠抚摸或母婴分离来确定WKY大鼠表型的各个方面是否可被早期生活因素改变。我们首先在旷场试验、高架十字迷宫、新奇抑制摄食试验、社交互动试验和强迫游泳试验（FST）中比较了WKY大鼠与Sprague-Dawley（SD）大鼠、Wistar大鼠和自发性高血压（SHR）大鼠的行为。WKY大鼠在FST中表现出较高的基线不动时间，并且是唯一在FST第2天与第1天相比不动时间增加的品系（习得性无助的指标）。与其他品系相比，WKY大鼠还表现出更大的社交回避，以及肾上腺和心脏增大。接下来，我们测试了新生鼠抚摸或早期生活母婴分离应激是否会影响WKY大鼠的行为。这两种操作都没有影响它们的焦虑和抑郁样行为，这可能是由于其表型有强大的遗传基础。我们的研究结果表明，WKY大鼠是一个有用的模型，它捕捉到了与临床抑郁症相关的特定功能领域，包括：精神运动迟缓、行为抑制、习得性无助、社交退缩和生理功能障碍。WKY大鼠似乎对在其他品系中具有治疗作用的早期生活操作（即新生鼠抚摸）具有抗性，并且可能是开发针对难治性抑郁症的个性化抗抑郁疗法的有用模型。
