Department of Psychology, Arizona State University, Tempe, Arizona 85287-1104, USA.
Learn Mem. 2020 Jul 15;27(8):319-327. doi: 10.1101/lm.051060.119. Print 2020 Aug.
Chronic stress typically leads to deficits in fear extinction when tested soon after chronic stress ends. Given the importance of extinction in updating fear memories, the current study examined whether fear extinction was impaired in rats that were chronically stressed and then given a break from the end of chronic stress to the start of fear conditioning and extinction. Male rats were chronically stressed by restraint (6 h/d/21 d) and tested soon (termed immediate, STR-IMM), or 3 or 6 wk after a rest period from restraint (termed rest or "R," STR-R3, STR-R6). In Experiment 1, STR-R3 and STR-R6 discriminated between the cue and nonshock context better than STR-IMM or control. Interestingly, STR-IMM showed high freezing to the nonshock context. Consequently, Experiment 2 investigated whether STR-IMM generalized across contexts, which was not supported. Experiment 3 determined whether STR-IMM were susceptible to second-order conditioning to a novel context, but showed that the level of second-order conditioning was similar for all groups. These findings reveal that rats exposed to chronic stress and then given a rest period of 3 or 6 wk, express unique fear extinction profiles compared to control and STR-IMM. Specifically, STR-R demonstrated excellent cue and context discrimination during extinction, and perhaps showed a stress inoculation effect. For STR-IMM, the heightened freezing under these extensive acclimation parameters was not attributed to generalization nor to second-order fear conditioning to "safe" contexts and, instead, may reflect hypervigilance.
慢性应激通常会导致慢性应激结束后不久进行的恐惧消退缺陷。鉴于消退在更新恐惧记忆中的重要性，本研究检查了慢性应激后休息一段时间，然后开始进行恐惧条件反射和消退的大鼠是否存在恐惧消退受损的情况。雄性大鼠通过束缚（6 h/d/21 d）进行慢性应激，并在应激结束后立即（称为即时，STR-IMM）或 3 或 6 周后（称为休息或“R”，STR-R3，STR-R6）进行测试。在实验 1 中，STR-R3 和 STR-R6 比 STR-IMM 或对照组更好地区分线索和非冲击环境。有趣的是，STR-IMM 对非冲击环境表现出高冻结。因此，实验 2 研究了 STR-IMM 是否会跨环境泛化，结果不支持这一点。实验 3 确定 STR-IMM 是否容易受到新环境的二阶条件作用，但表明所有组的二阶条件作用水平相似。这些发现表明，与对照组和 STR-IMM 相比，暴露于慢性应激并随后休息 3 或 6 周的大鼠表现出独特的恐惧消退特征。具体而言，STR-R 在消退期间表现出出色的线索和环境辨别能力，并且可能表现出应激接种效应。对于 STR-IMM，在这些广泛的适应参数下的高度冻结不是归因于泛化，也不是归因于对“安全”环境的二阶恐惧条件作用，而是可能反映出高度警惕。
