Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy.
Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy.
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DOI：
10.1177/23982128211015110
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发表时间：
2021-01
影响因子：
--
通讯作者：
Robinson ESJ
中科院分区：
文献类型：
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作者：
Jackson MG;Lightman SL;Gilmour G;Marston H;Robinson ESJ
冷漠在神经系统疾病或病毒感染后的患者中被广泛报道，但也见于其他健康的老年人。这项研究调查了老年雄性小鼠是否表达与冷漠表型相关的行为和生理变化。使用奖励工作的动机的措施，我们发现赤字的累进比率任务有关的反应速度。在与努力相关的决策任务中，老年小鼠不太愿意为高价值奖励而付出努力。老年小鼠表现出降低奖励敏感性，但也降低了措施的焦虑，在新奇的抑制喂养试验和衰减反应的约束压力，降低皮质酮和室旁核c-fos激活。这种情感变化的特征与抑郁症模型中观察到的不一致，但表明情绪迟钝。在认知测试（新物体识别）中，老年小鼠没有表现出障碍，但在新环境中探索的活动较低。总而言之，这些数据表明老年小鼠在动机行为、奖励敏感性和情绪反应等领域都表现出变化，可能是冷漠精神症状临床前研究的合适模型。
Apathy is widely reported in patients with neurological disorders or post viral infection but is also seen in otherwise-healthy aged individuals. This study investigated whether aged male mice express behavioural and physiological changes relevant to an apathy phenotype. Using measures of motivation to work for reward, we found deficits in the progressive ratio task related to rate of responding. In an effort-related decision-making task, aged mice were less willing to exert effort for high value reward. Aged mice exhibited reduced reward sensitivity but also lower measures of anxiety in the novelty supressed feeding test and an attenuated response to restraint stress with lower corticosterone and reduced paraventricular nucleus c-fos activation. This profile of affective changes did not align with those observed in models of depression but suggested emotional blunting. In a test of cognition (novel object recognition), aged mice showed no impairments, but activity was lower in a measure of exploration in a novel environment. Together, these data suggest aged mice show changes across the domains of motivated behaviour, reward sensitivity and emotional reactivity and may be a suitable model for the pre-clinical study of the psychiatric symptom of apathy.