Probing the motivational circuitry of binge eating.
Probing the motivational circuitry of binge eating.
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探究暴饮暴食的动机回路。
DOI：
10.1038/s41386-019-0568-4
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Calu,DonnaJ
中科院分区：
文献类型：
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作者：
Martin,DavidA;Calu,DonnaJ
在过去的四十年里，肥胖率的稳步上升需要“食物成瘾”的临床前模型，这些模型准确地放弃了暴饮暴食的心理特征。神经生物学研究对于理解过度食用热量密集和美味食物所发生的动机和激素失调至关重要。在这一期的《神经精神药理学》中，Spierling等人仔细考虑了食物成瘾的诊断特征，以开发和验证间歇性获得可口食物寻求模型的一种变体中的动机结构。在确定了一个发展出强迫性觅食行为的大鼠亚组后，作者研究了相关的激素谱和皮质纹状体通路参与[1]。通过扩展他们先前开发的模型[2，3]，Spierling等人借鉴了药物自我给药文献，旨在检查短暂与长时间间歇性接触高度可口的饮食对雌性大鼠出现强迫样动机的影响。经典的强迫性测量包括药物不可用时持续寻求药物（在无药物期间做出反应），高动机（增加的进展比率反应），以及尽管有害后果仍继续做出反应（休克惩罚反应）。在此，Spierling等人确定了间歇性暴露于高可口食物的大鼠亚组中出现的强迫样行为[1]。作者使用了四个实验组，包括连续进入仅咀嚼组，连续进入优选的高蔗糖营养完整饮食（适口），间歇性进入适口饮食组，每48小时进入适口饮食30分钟，以及长时间进入间歇性进入适口饮食组，每48小时进入适口饮食24小时。与之前的研究一致[3，5-7]，大鼠在间歇性可获得的情况下以高水平食用可口的饲料，并且在仅可获得饲料的期间限制饲料食用。在研究人员探索杠杆挤压食物的动机的日子里，间歇性适口大鼠在自我给药阶段开始时获得了适口的食物，而连续进食组和适口组在器械给药阶段周围的几个小时内获得了各自的饮食。与他们之前的研究[2]保持一致，作者为间歇组提供了与他们用于工具性饮食相同的可口颗粒，这防止了在操作背景下产生负对比效应的可能性[8，9]。与连续访问组杠杆按各自的饮食相比，两个间歇组表现出一致较高的固定比率（FR）响应，超时响应，和渐进比率（PR）响应。间歇性组的自愿食物限制可能导致他们的更高水平的可口的颗粒自我管理相比，连续访问组自我管理各自的饮食。总的来说，无障碍访问组表现出对可口食物的动机增加。然而，当测试持续反应，尽管有不利的后果（每三个饥饿者在FR时间表产生了休克），只有一个子集的惩罚抵抗大鼠从不受欢迎的访问组继续按可口的饮食。因此，个体差异与时间安排效应相结合，在大鼠的一个子集中产生了强迫样表型，类似于以前使用可卡因作为兴奋剂的结果[4]。高瘦素和低生长激素释放肽的激素水平与一个人的激励措施相关。
The steady increase in obesity rates over the past four decades necessitates preclinical models of “food addiction” that accurately capitulate the psychological hallmarks of overeating. Neurobiological inquiry is critical to understand the motivational and hormonal dysregulation that occurs with overconsumption of calorically dense and palatable foods. In this issue of Neuropsychopharmacology, Spierling et al. carefully considered diagnostic features of food addiction to develop and validate motivational constructs in a variant of the intermittent access to palatable food-seeking model. After identifying a subset of rats that develop compulsive-like foodseeking behavior, the authors studied the associated hormonal profiles and corticostriatal pathway involvement [1]. By extending their previously developed model [2, 3], Spierling et al. draw from drug self-administration literature, aiming to examine the effect of brief versus long intermittent access to highly palatable diet exposure on the emergence of compulsive-like motivation in female rats. Classic compulsivity measures include persistence of drug seeking when the drug is unavailable (responding during no-drug periods), high motivation (increased progressive-ratio responding), and continued responding despite harmful consequences (shockpunished responding)[4]. Here, Spierling et al. identified the compulsive-like behaviors arising in a subset of rats exposed intermittently to highly palatable food [1]. The authors used four experimental groups, including a continuous access to chow-only group, a continuous access to the preferred, high-sucrose, nutritionally complete diet (palatable), a brief-access intermittent group with 30 min of access to the palatable diet every 48 h, and a long-access intermittent group with 24 h of access to the palatable diet every 48 h. Consistent with prior studies [3, 5–7], rats consumed the palatable diet at high levels when it was intermittently available and restricted chow consumption during periods when only chow was available. On days that investigators probed motivation to lever press for food, intermittent palatable rats gained access to palatable food at the start of the self-administration session, while continuous chow and palatable groups had access to their respective diets in the hours surrounding the instrumental session. Keeping with their prior study [2], the authors provided the intermittent groups with the same palatable pellets for the homecage-palatable diet as they used for the instrumental reinforcer, which prevented the potential for negative-contrast effects in the operant context [8, 9]. Compared with continuous-access groups lever pressing for their respective diets, the two intermittent groups exhibited uniformly higher fixed-ratio (FR) responding, timeout responding, and progressive ratio (PR) responding. The voluntary chow restriction in intermittent groups may have contributed to their greater levels of palatable pellet self-administration compared with continuous-access groups self-administering their respective diets. Collectively, the intermittent-access groups exhibited increased motivation for the palatable food. However, when testing for continued responding despite adverse consequences (every third reinforcer during the FR schedule produced a shock), only a subset of punishment-resistant rats from intermittent-access groups continued to press for the palatable diet. Thus, individual differences coupled with scheduling effects combined to produce a compulsive-like phenotype in a subset of rats, akin to previous results using cocaine as the reinforcer [4]. Hormonal profiles indicative of high leptin and low ghrelin correlated with motivational measures in a …