Ponomareva Olga Y, Fenster Robert J, Ressler Kerry J
McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Curr Top Behav Neurosci. 2023;64:289-305. doi: 10.1007/7854_2023_443.
Extinction is the process by which the memory of a learned conditioned association decreases over time and with introduction of new associations. It is a vital part of fear learning, and it is critical to recovery in multiple fear-related disorders, including Specific and Social Phobias, Panic Disorder, Obsessive Compulsive Disorder (OCD), and Posttraumatic Stress Disorder (PTSD). The process of extinction is also the underlying mechanism for recovery in gold-standard therapies for PTSD, including prolonged exposure, cognitive processing therapy, eye movement desensitization and procession, as well as other empirically-based paradigms. Pharmacological modulators of extinction are thus promising targets for treatment of fear-related disorders. We focus here on emerging psychopharmacological treatments to facilitate extinction: D-cycloserine, scopolamine, losartan, ketamine, and 3,4-methylenedioxymethamphetamine. We also provide an overview of recent advances in molecular pathways that show promise as targets for extincion and inhibitory learning, including pathways related to cannabinoid, brain-derived neurotrophic factor, hypothalamic-pituitary-adrenal signaling, and promising work in neurosteroid compounds.
消退是指习得的条件性关联记忆随着时间推移以及新关联的引入而逐渐减少的过程。它是恐惧学习的重要组成部分，对于多种与恐惧相关的疾病的恢复至关重要，这些疾病包括特定恐惧症和社交恐惧症、惊恐障碍、强迫症（OCD）以及创伤后应激障碍（PTSD）。消退过程也是PTSD金标准疗法恢复的潜在机制，这些疗法包括延长暴露疗法、认知加工疗法、眼动脱敏再处理疗法以及其他基于经验的范式。因此，消退的药理学调节剂有望成为治疗与恐惧相关疾病的靶点。我们在此重点关注促进消退的新兴精神药理学治疗方法：D-环丝氨酸、东莨菪碱、氯沙坦、氯胺酮和3,4-亚甲基二氧甲基苯丙胺。我们还概述了分子途径的最新进展，这些途径有望成为消退和抑制性学习的靶点，包括与大麻素、脑源性神经营养因子、下丘脑-垂体-肾上腺信号传导相关的途径，以及神经甾体化合物方面的有前景的研究工作。
