School of Psychology, The University of New South Wales, Sydney, Australia.
School of Psychology, The University of New South Wales, Sydney, Australia.
Neurobiol Learn Mem. 2018 Nov;155:344-350. doi: 10.1016/j.nlm.2018.09.004. Epub 2018 Sep 5.
Phenotypic differences in conditioned fear expression may be a marker of vulnerability to the development of anxiety disorders. Hippocampal FGF2 correlates negatively with conditioned fear expression, and antidepressants, the first-line pharmacological treatment for anxiety, increase hippocampal FGF2. In the present study, we assessed whether treatment with the selective serotonin reuptake inhibitor fluoxetine reduces conditioned fear expression in rats that naturally express lower (Low fear) or higher (High fear) levels of fear following a single-trial conditioning session. Experiment 1 demonstrated that phenotypic differences in fear expression were highly stable over a two-week interval. Experiment 2 demonstrated that two weeks of fluoxetine treatment (administered via drinking water) reduced conditioned fear expression in both Low and High fear rats. Experiment 3 demonstrated that two weeks of fluoxetine reduced conditioned fear expression even when treatment commenced two weeks after fear conditioning, but not when conditioned fear was assessed following a two-week drug-free washout period. Additionally, fluoxetine increased hippocampal FGF2 levels relative to vehicle-treated rats, but only when measured immediately after fluoxetine treatment, and not two weeks after treatment termination. Together, these results provide further indirect evidence that endogenous hippocampal FGF2 may mediate individual differences in conditioned fear expression. They also suggest that fluoxetine may be effective in reducing conditioned fear expression in both vulnerable and resilient populations when administered immediately, or sometime after, aversive experiences, but these effects do not persist once treatment is terminated.
条件性恐惧表达的表型差异可能是易患焦虑障碍发展的标志物。海马 FGF2 与条件性恐惧表达呈负相关，而抗抑郁药是焦虑的一线药物治疗方法，可增加海马 FGF2。在本研究中，我们评估了选择性 5-羟色胺再摄取抑制剂氟西汀是否会降低在单次训练后自然表现出较低（低恐惧）或较高（高恐惧）恐惧水平的大鼠的条件性恐惧表达。实验 1 表明，恐惧表达的表型差异在两周的间隔内高度稳定。实验 2 表明，两周的氟西汀治疗（通过饮用水给予）可降低低恐惧和高恐惧大鼠的条件性恐惧表达。实验 3 表明，即使在恐惧条件作用后两周开始治疗，而不是在两周无药物洗脱期后评估条件性恐惧时，氟西汀也能降低条件性恐惧表达。此外，与接受载体治疗的大鼠相比，氟西汀增加了海马 FGF2 水平，但仅在氟西汀治疗后立即测量时，而不是在治疗结束后两周测量时。总之，这些结果提供了进一步的间接证据，表明内源性海马 FGF2 可能介导条件性恐惧表达的个体差异。它们还表明，氟西汀在经历厌恶体验后立即或一段时间后给予，可能对易感性和弹性人群的条件性恐惧表达有效，但一旦停止治疗，这些效果就不会持续。
