Behavioral Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Philipps-University of Marburg, Gutenberg-Str. 18, D-35032 Marburg, Germany.
Associative Learning, Experimental and Biological Psychology, Faculty of Psychology, Philipps-University of Marburg, Gutenberg-Str. 18, D-35032 Marburg, Germany.
Int J Mol Sci. 2021 Jun 30;22(13):7088. doi: 10.3390/ijms22137088.
Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality.
焦虑症与未能充分消除恐惧记忆有关。5-羟色胺能系统（5-羟色胺，5-HT）及其 5-羟色胺转运体（5-HTT，SERT）强烈参与焦虑和恐惧的调节。在本研究中，我们在雄性和雌性大鼠的差异恐惧条件反射范式中，检查了 SERT 缺乏对恐惧消退的影响。通过测量不动性和警报 22-kHz 超声发声（USV）的数量来测量获得、消退和恢复期间的恐惧相关行为。个体差异的特质性新奇寻求、焦虑相关行为、习惯化学习、认知表现和疼痛敏感性的预测价值，用于预测恐惧消退。我们的结果表明，SERT 缺乏强烈影响差异恐惧条件反射过程中的 22-kHz USV 发射。在获得、消退和恢复期间，SERT 缺乏一致导致 22-kHz USV 发射减少。虽然 SERT 缺乏不影响获得期间的不动性，但基因型差异在消退期间开始出现，并且缺乏 SERT 的恢复大鼠表现出比野生型同窝对照更高水平的不动性。恢复表现为不动性水平增加，但 22-kHz USV 发射没有增加。明显的性别差异很明显。在几种个体差异的特质性测量中，焦虑相关行为具有最佳的预测质量。
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