Universidade Federal de Mato Grosso do Sul, Três Lagoas, MS, Brazil; Rede Brasileira de Estudos de Memória (ReBraEM), Brazil.
Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil; Rede Brasileira de Estudos de Memória (ReBraEM), Brazil.
Neurosci Biobehav Rev. 2023 Apr;147:105101. doi: 10.1016/j.neubiorev.2023.105101. Epub 2023 Feb 17.
Fear conditioning and avoidance tasks usually elicit adaptive aversive memories. Traumatic memories are more intense, generalized, inflexible, and resistant to attenuation via extinction- and reconsolidation-based strategies. Inducing and assessing these dysfunctional, maladaptive features in the laboratory are crucial to interrogating posttraumatic stress disorder's neurobiology and exploring innovative treatments. Here we analyze over 350 studies addressing this question in adult rats and mice. There is a growing interest in modeling several qualitative and quantitative memory changes by exposing already stressed animals to freezing- and avoidance-related tests or using a relatively high aversive training magnitude. Other options combine aversive/fearful tasks with post-acquisition or post-retrieval administration of one or more drugs provoking neurochemical or epigenetic alterations reported in the trauma aftermath. It is potentially instructive to integrate these procedures and incorporate the measurement of autonomic and endocrine parameters. Factors to consider when defining the organismic and procedural variables, partially neglected aspects (sex-dependent differences and recent vs. remote data comparison) and suggestions for future research (identifying reliable individual risk and treatment-response predictors) are discussed.
恐惧条件作用和回避任务通常会引起适应性的厌恶记忆。创伤记忆更强烈、更广泛、更僵化，并且难以通过基于消退和再巩固的策略来减弱。在实验室中诱导和评估这些功能失调和适应不良的特征对于探究创伤后应激障碍的神经生物学和探索创新治疗方法至关重要。在这里，我们分析了超过 350 项针对成年大鼠和小鼠的研究，这些研究都涉及到这个问题。人们越来越感兴趣的是通过使已经受到压力的动物暴露于与冻结和回避相关的测试中，或者使用相对较高的厌恶训练强度来模拟几种定性和定量的记忆变化。其他选择是将厌恶/恐惧任务与药物的给药相结合，这些药物会引起创伤后报告的神经化学或表观遗传改变，这些药物可在获取后或检索后给药。将这些程序整合起来，并测量自主和内分泌参数可能具有启发性。讨论了在定义机体和程序变量时需要考虑的因素、部分被忽视的方面（性别依赖性差异和近期与远期数据比较）以及对未来研究的建议（确定可靠的个体风险和治疗反应预测因子）。
