Behavioral and Neural Effects of Activity-Based Anorexia

神经性厌食症是一种复杂的进食障碍，其部分特征是吞咽不足、饮食模式紊乱、体重减轻、多动和下丘脑-垂体-性腺轴失调。约90%的确诊病例涉及女性。神经性厌食症的症状治疗是有限的，因为我们缺乏了解的多种因素背后的这种复杂的障碍。动物研究表明，限制进食并让雌性大鼠自由进入跑步轮后，会出现进食减少、体重迅速下降、跑步轮活动增加和卵巢生殖功能紊乱的现象。由于这些症状与神经性厌食症的症状相似，这种模式已被用作神经性厌食症的动物模型。本研究的目的是利用这种动物模型来研究(a)患有活动性厌食症的雌性大鼠的自发进食模式，(b)雌二醇是否调节对活动性厌食症的敏感性，以及(c)患有活动性厌食症的雌性大鼠的食物刺激神经元激活模式。雌性大鼠将被安置在定制设计的笼子里，允许持续监测自发进食和跑动轮活动。我们将在去卵巢大鼠中研究雌二醇对运动性厌食症的影响。最后，c- Fos免疫组织化学将用于观察食物刺激下神经元活动的变化。本研究将提供有关活动性厌食症的行为、激素和神经基础的新信息，从而为未来研究活动性厌食症的机制奠定基础。这项研究的长期目标是确定神经性厌食症的神经化学基础，希望这可能导致更有效的药物治疗和干预计划的发展。

Anorexia nervosa is a complex eating disorder characterized in part by hypophagia, disorganized eating patterns, body weight loss, hyperactivity, and a dysregulation of the hypothalamic-pituitary-gonadal axis. About 90% of diagnosed cases involve women. Therapeutic treatment of the symptoms of anorexia nervosa is limited due to our lack of understanding of the multiple factors underlying this complex disorder. Animal studies have shown that female rats maintained on a food restriction schedule and given free access to running wheels display hypophagia, rapid body weight loss, increased running wheel activity, and a disruption of ovarian reproductive function. Because these symptoms are similar to the symptoms of anorexia nervosa, this paradigm has been used as an animal model of anorexia nervosa. The aim of this proposal is to use this animal-based model to investigate (a) the spontaneous feeding patterns of female rats with activity-based anorexia, (b) whether estradiol modulates susceptibility to activity-based anorexia, and (c) the patterns of meal-stimulated neuronal activation in female rats with activity-based anorexia: Female rats will be housed in custom-designed cages that permit the continual monitoring of spontaneous feeding and running wheel activity. The effects of estradiol on the development of activity-based anorexia will be investigated in ovariectomized rats with and without estradiol replacement. Finally, c- Fos immunohistochemistry will be used to visualize changes in meal- stimulated neuronal activity. This research will provide novel information regarding the behavioral, hormonal, and neural substrates of activity-based anorexia and will, therefore, provide a foundation for future experiments investigating the mechanism underlying activity- based anorexia. A long-term goal of this research effort is to identify the neurochemical substrate underlying anorexia nervosa in the hope that this may lead to the development of more effective pharmacotherapeutic treatments and intervention programs.