Elevated anxiety often precedes anorexia nervosa and persists after weight restoration. Patients with anorexia nervosa often describe self-starvation as pleasant, potentially because food restriction can be anxiolytic. Here, we tested whether repeated stress can cause animals to prefer a starvation-like state. We developed a virtual reality place preference paradigm in which head-fixed mice can voluntarily seek a starvation-like state induced by optogenetic stimulation of hypothalamic agouti-related peptide (AgRP) neurons. Prior to stress exposure, males but not females showed a mild aversion to AgRP stimulation. Strikingly, following multiple days of stress, a subset of females developed a strong preference for AgRP stimulation that was predicted by high baseline anxiety. Such stress-induced changes in preference were reflected in changes in facial expressions during AgRP stimulation. Our study suggests that stress may cause females predisposed to anxiety to seek a starvation state and provides a powerful experimental framework for investigating the underlying neural mechanisms.

中文翻译：

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反复的压力会促使易焦虑的雌性小鼠寻求类似饥饿的状态


焦虑加剧通常先于神经性厌食症，并在体重恢复后持续存在。神经性厌食症患者经常形容自我饥饿是令人愉快的，可能是因为限制食物可以缓解焦虑。在这里，我们测试了反复的压力是否会导致动物更喜欢类似饥饿的状态。我们开发了一种虚拟现实位置偏好范例，其中头部固定的小鼠可以自愿寻求由下丘脑刺鼠相关肽（AgRP）神经元的光遗传学刺激诱导的饥饿样状态。在暴露于压力之前，男性而非女性对 AgRP 刺激表现出轻微的厌恶。引人注目的是，经过多天的压力后，一部分女性对 AgRP 刺激产生了强烈的偏好，这是由高基线焦虑所预测的。这种压力引起的偏好变化反映在 AgRP 刺激期间面部表情的变化上。我们的研究表明，压力可能会导致女性容易焦虑，寻求饥饿状态，并为研究潜在的神经机制提供了一个强大的实验框架。