Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?
Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?
复制标题
DOI：
10.1186/1741-7007-4-8
复制
发表时间：
2006-04-13
期刊：
影响因子：
5.4
通讯作者：
Berridge KC
中科院分区：
文献类型：
--
作者：
Peciña S;Schulkin J;Berridge KC
促肾上腺皮质激素释放因子（CRF）通常被认为是介导压力，恐惧和焦虑的厌恶方面。然而，脑中的CRF释放也是由自然奖励和激励线索引起的，这增加了脑中某些CRF系统介导积极激励动机的独立功能的可能性，例如放大激励显著性。在这里，我们问激活的边缘CRF子系统是否放大了积极的奖励动机引起的奖励线索先前与奖励，在某种程度上，可能会加剧线索触发的暴食追求食物或其他激励？我们评估的影响，CRF微注射到内侧壳的丘脑核使用一个纯粹的激励版本的巴甫洛夫-工具转移，一个措施特别敏感的奖励线索的激励显着性（它分离的影响，厌恶的压力，压力减轻，挫折和其他传统的解释压力增加的行为）。首先训练大鼠按下两个杠杆中的一个以获得蔗糖颗粒，然后分别调节以将巴甫洛夫线索与游离蔗糖颗粒相关联。在试验日，大鼠接受微量注射溶媒、CRF（250或500 ng/0.2 μl）或苯丙胺（20 μg/0.2 μl）。在半小时的测试中，在存在或不存在巴甫洛夫线索的情况下评估杠杆按压。显微注射最高剂量的CRF（500 ng）或安非他明（20 μg）选择性地增强了巴甫洛夫奖赏线索的能力，以触发蔗糖奖赏的工具性能增加的阶段性峰值，每个峰值持续一分钟左右，然后在线索后衰减。杠杆按下没有增强CRF微量注射在基线的巴甫洛夫线索或在演示过程中没有线索，表明CRF增强不能解释为结果的广义运动觉醒，挫折或压力，或持续试图改善厌恶状态。我们的结论是，CRF核壳放大积极的动机线索奖励，特别是通过放大激励显着性，归因于巴甫洛夫线索以前与这些奖励。CRF诱导的激励显著性放大提供了一个新的解释，为什么压力可能会产生线索触发暴饮暴食，毒瘾复发，或其他过度追求奖励的爆发。
Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl) or amphetamine (20 μg/0.2 μl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 μg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards.