Wright Rebecca L, Gilmour Gary, Dwyer Dominic M
School of Psychology, Cardiff University, Cardiff, United Kingdom.
Lilly Research Centre, Eli Lilly & Co. Ltd., Erl Wood Manor, United Kingdom.
Front Behav Neurosci. 2020 Jun 3;14:70. doi: 10.3389/fnbeh.2020.00070. eCollection 2020.
The Wistar Kyoto (WKY) rat has been proposed as a model of depression-like symptoms. However, anhedonia-a reduction in the response to normatively rewarding events-as a central depression symptom has yet to be fully assessed in this model. We compared WKY rats and Wistar controls, with stress-susceptibility examined by applying mild unpredictable stress to a subset of each group. Anhedonia-like behavior was assessed using microstructural analysis of licking behavior, where mean lick cluster size reflects hedonic responses. This was combined with tests of anticipatory contrast, where the consumption of a moderately palatable solution (4% sucrose) is suppressed in anticipation of a more palatable solution (32% sucrose). WKY rats displayed greatly attenuated hedonic reactions to sucrose overall, although their reactions retained some sensitivity to differences in sucrose concentration. They displayed normal reductions in consumption in anticipatory contrast, although the effect of contrast on hedonic reactions was greatly blunted. Mild stress produced overall reductions in sucrose consumption, but this was not exacerbated in WKY rats. Moreover, mild stress did not affect hedonic reactions or the effects of contrast. These results confirm that the WKY substrain expresses a direct behavioral analog of anhedonia, which may have utility for increasing mechanistic understanding of depression symptoms.
Wistar Kyoto(WKY)大鼠已被提议作为类似抑郁症状的模型。然而,作为抑郁症核心症状的快感缺失——对正常奖励事件反应的减少——在该模型中尚未得到充分评估。我们比较了WKY大鼠和Wistar对照大鼠,通过对每组中的一部分施加轻度不可预测应激来检测应激易感性。使用舔舐行为的微观结构分析评估类似快感缺失的行为,其中平均舔舐簇大小反映享乐反应。这与预期对比测试相结合,在预期更美味的溶液(32%蔗糖)时,中等美味溶液(4%蔗糖)的消耗量会受到抑制。总体而言,WKY大鼠对蔗糖的享乐反应大大减弱,尽管它们的反应对蔗糖浓度差异仍保留一些敏感性。它们在预期对比中显示出正常的消耗量减少,尽管对比对享乐反应的影响大大减弱。轻度应激导致蔗糖消耗量总体减少,但在WKY大鼠中并未加剧。此外,轻度应激不影响享乐反应或对比效应。这些结果证实,WKY亚系表现出快感缺失的直接行为类似物,这可能有助于增强对抑郁症状的机制理解。