PDF(Pubmed)
Abstract：
UNASSIGNED: Clinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors.
UNASSIGNED: Apprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food.
UNASSIGNED: We consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food.
UNASSIGNED: Results indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.
Anxiety disorders have a complex etiology that is difficult to study in laboratory animals because most laboratory manipulations do not induce a chronic, generalized condition analogous to the clinical disorder. Here, laboratory mice developed approach-avoidance conflicts when a response was unpredictably rewarded or punished. These conditions (but not predictable outcomes) promoted a long-lasting general increase in a range of behaviors and stress hormones that reflect underlying anxiety, and remedial exposure to predictable conditions of reward and punishment ameliorated the generalized state. These results represent the development of a conceptually valid animal model for the study of anxiety and suggest conditions that can contribute to the etiology and treatment of anxiety.
UNASSIGNED: Apprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food.
UNASSIGNED: We consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food.
UNASSIGNED: Results indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.
Anxiety disorders have a complex etiology that is difficult to study in laboratory animals because most laboratory manipulations do not induce a chronic, generalized condition analogous to the clinical disorder. Here, laboratory mice developed approach-avoidance conflicts when a response was unpredictably rewarded or punished. These conditions (but not predictable outcomes) promoted a long-lasting general increase in a range of behaviors and stress hormones that reflect underlying anxiety, and remedial exposure to predictable conditions of reward and punishment ameliorated the generalized state. These results represent the development of a conceptually valid animal model for the study of anxiety and suggest conditions that can contribute to the etiology and treatment of anxiety.
摘要：
■临床焦虑是一种普遍的状态，其特征是担心期望的感觉，与恐惧或压力等瞬时反应不同。相比之下,大多数焦虑的实验室测试集中在对瞬时压力源的急性反应。
通过对小鼠(18天)进行操作,其中运行反应(实验1)或条件刺激(实验2)不可预测地与奖励(食物)或惩罚(脚击)配对,诱导忧虑期望。在这种治疗之前，在开放视野和光/暗箱中对小鼠进行测试，以评估被断言反映状态焦虑的瞬时反应。治疗后,在高架迷宫中评估小鼠的状态焦虑，社交互动测试，惊吓反应测试,侵入性物体掩埋试验，和应激诱导的皮质酮升高。在实验3中，我们与实验1相似地处理小鼠，但经过混合价训练，一些老鼠没有接受额外的训练，额外的混合价训练，或者被转移到与食物一致的(可预测的)强化。
■在经历了混合价不可预测的强化之后，我们一致观察到焦虑样行为的增加。混合价训练后，这种广泛性焦虑持续了至少4周，如果混合价训练后再进行可预测的食物强化，则可以逆转。
■结果表明，具有不可预测的奖励/惩罚的经验可以诱发类似于广泛性焦虑的慢性状态，可以通过暴露于稳定状态来缓解，可预测的条件。这种学习的忧虑方案为研究实验动物焦虑的病因和治疗提供了概念上有效的模型。
焦虑症具有复杂的病因，难以在实验动物中研究，因为大多数实验室操作不会诱发慢性焦虑症，类似于临床疾病的全身性病症。这里,当反应得到不可预测的奖励或惩罚时,实验小鼠产生了回避冲突.这些情况（但不可预测的结果）促进了一系列行为和压力荷尔蒙的长期普遍增加，这些行为和压力荷尔蒙反映了潜在的焦虑，在可预测的奖励和惩罚条件下的补救暴露改善了普遍的状态。这些结果代表了用于焦虑研究的概念上有效的动物模型的发展，并表明了可能有助于焦虑的病因和治疗的条件。
通过对小鼠(18天)进行操作,其中运行反应(实验1)或条件刺激(实验2)不可预测地与奖励(食物)或惩罚(脚击)配对,诱导忧虑期望。在这种治疗之前，在开放视野和光/暗箱中对小鼠进行测试，以评估被断言反映状态焦虑的瞬时反应。治疗后,在高架迷宫中评估小鼠的状态焦虑，社交互动测试，惊吓反应测试,侵入性物体掩埋试验，和应激诱导的皮质酮升高。在实验3中，我们与实验1相似地处理小鼠，但经过混合价训练，一些老鼠没有接受额外的训练，额外的混合价训练，或者被转移到与食物一致的(可预测的)强化。
■在经历了混合价不可预测的强化之后，我们一致观察到焦虑样行为的增加。混合价训练后，这种广泛性焦虑持续了至少4周，如果混合价训练后再进行可预测的食物强化，则可以逆转。
■结果表明，具有不可预测的奖励/惩罚的经验可以诱发类似于广泛性焦虑的慢性状态，可以通过暴露于稳定状态来缓解，可预测的条件。这种学习的忧虑方案为研究实验动物焦虑的病因和治疗提供了概念上有效的模型。
焦虑症具有复杂的病因，难以在实验动物中研究，因为大多数实验室操作不会诱发慢性焦虑症，类似于临床疾病的全身性病症。这里,当反应得到不可预测的奖励或惩罚时,实验小鼠产生了回避冲突.这些情况（但不可预测的结果）促进了一系列行为和压力荷尔蒙的长期普遍增加，这些行为和压力荷尔蒙反映了潜在的焦虑，在可预测的奖励和惩罚条件下的补救暴露改善了普遍的状态。这些结果代表了用于焦虑研究的概念上有效的动物模型的发展，并表明了可能有助于焦虑的病因和治疗的条件。
