Santa Lucia Foundation, European Centre for Brain Research (CERC), via del Fosso di Fiorano 64, Rome 00143 Italy.
BMC Neurosci. 2010 Feb 8;11:15. doi: 10.1186/1471-2202-11-15.
Eating disorders are multifactorial psychiatric disorders. Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. Although compulsive behavior is considered to characterize pathological excessive food intake, to our knowledge, no evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior. Brain monoamine transmission is considered to have a key role in vulnerability to eating disorders, and norepinephrine in medial prefrontal cortex has been shown to be critical for food-related motivated behavior.Here, using a new paradigm of conditioned suppression, we investigated whether the ability of a foot-shock-paired conditioned stimulus to suppress chocolate-seeking behavior was reversed by previous exposure to a food restriction experience, thus modeling food seeking in spite of harmful consequences in mice. Moreover, we assessed the effects of selective norepinephrine inactivation in medial prefrontal cortex on conditioned suppression test in stressed and caloric restricted mice.
While Control (non food deprived) animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food restricted animals showed food seeking/intake despite its possible harmful consequences. Moreover, food seeking in spite of harmful consequences was prevented by selective norepinephrine inactivation, thus showing that prefrontal cortical norepinephrine is critical also for maladaptive food-related behavior.
These findings indicate that adaptive food seeking/intake can be transformed into maladaptive behaviors and point to "top-down" influence on eating disturbances and to new targets for therapy of aberrant eating behaviors.
饮食失调是一种多因素的精神疾病。慢性应激体验和热量限制是人类和动物饮食失调的最有力触发因素。尽管强迫行为被认为是病理性过量进食的特征，但据我们所知，尽管可能有潜在的有害后果，但没有证据表明持续的食物寻求/摄入，这是强迫行为的一个指标。脑单胺传递被认为在易患饮食失调方面起着关键作用，而内侧前额叶皮质中的去甲肾上腺素已被证明对与食物相关的动机行为至关重要。在这里，我们使用条件抑制的新范式，研究了以前暴露于食物限制体验是否会逆转与足部电击相关的条件刺激抑制巧克力寻求的能力，从而在老鼠中模拟尽管有害后果仍在寻求食物。此外，我们评估了内侧前额叶皮质中选择性去甲肾上腺素失活对应激和热量限制小鼠条件抑制测试的影响。
虽然对照（非食物剥夺）动物在呈现条件刺激时表现出对巧克力寻求的强烈条件抑制，但以前食物受限的动物仍表现出可能有害后果的食物寻求/摄入。此外，选择性去甲肾上腺素失活可防止有害后果的食物寻求，这表明前额叶皮质去甲肾上腺素对适应不良的食物相关行为也很关键。
这些发现表明，适应性的食物寻求/摄入可以转化为适应不良的行为，并指向对饮食失调的“自上而下”影响，以及治疗异常进食行为的新靶点。
