Department of Pharmacology,Institute of Neuroscience and Physiology,Sahlgrenska Academy,University of Gothenburg,Gothenburg,Sweden.
Acta Neuropsychiatr. 2019 Feb;31(1):46-51. doi: 10.1017/neu.2018.26. Epub 2018 Nov 8.
Whereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.
Male Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.
Noise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.
The data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.
尽管长期服用选择性 5-羟色胺再摄取抑制剂(SSRIs)对治疗焦虑症有效,但这些药物的急性给药可能会产生矛盾的焦虑作用。本研究旨在探讨 SSRIs 在非条件或有限条件性恐惧情况下的可能作用。
雄性 Sprague Dawley 大鼠在获得或表达情境条件性恐惧之前,给予单剂量的 SSRI(依他普仑),其中噪声爆发用作非条件刺激。冻结被评估为非条件恐惧(=对噪声爆发的急性反应)或条件恐惧(=对情境的反应)的指标。
噪声爆发引起了急性冻结反应增加,但在暴露 7 天后没有出现强烈的条件反应。在测试前给予依他普仑预处理,加重了非条件刺激呈现时的冻结反应,并揭示了条件反应;相比之下,在获得之前给予依他普仑预处理不会影响条件反应。
数据表明,无论动物的冻结是对所研究的刺激的急性非条件反应还是对同一刺激的条件反应,暴露于引起相对轻度恐惧的刺激的大鼠的冻结可能会因急性预处理 SSRI 而增强。