Enomoto Kosuke, Shibata Kazuro, Muraoka Hiroyuki, Kawano Masahiko, Inada Ken, Ishigooka Jun, Nishimura Katsuji, Oshibuchi Hidehiro
Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan.
Department of Psychiatry, Kitasato University, Sagamihara-shi, Kanagawa, Japan.
Neuropsychopharmacol Rep. 2024 Mar;44(1):197-205. doi: 10.1002/npr2.12418. Epub 2024 Feb 14.
Impairments in emotional memory are frequently observed in several mental disorders, highlighting their significance as potential therapeutic targets. Recent research on the cued fear conditioning model has elucidated the neural circuits involved in fear memory processing. However, contradictory findings have been reported concerning the role of dopamine and the impact of dopamine D2 receptor (D2R) antagonists. There is notably limited knowledge regarding the clinical utility of chronic D2R antagonist treatments. This study aimed to uncover how such treatments affect fear memory processing.
We utilized a cued fear conditioning rat model and conducted chronic haloperidol treatment for 14 days. Subsequently, to investigate the effect of chronic haloperidol treatment on fear-conditioned memory expression and extinction, we observed freezing behavior under exposure to a conditioned stimulus for 14 days.
Chronic haloperidol treatment suppressed freezing time on the fear memory expression. In contrast, a single haloperidol administration enhanced the freezing time on fear memory expression and delayed extinction.
The results of this study suggest that chronic administration of antipsychotic drugs affects fear memory processing differently from single-dose administration. This indicates that the effects of chronic D2R antagonist treatment are distinct from the nonspecific effects of the drugs. This study provides fundamental insights that may contribute to our understanding of therapeutic mechanisms for fear memory disorders related to D2R in the future.
在多种精神障碍中经常观察到情绪记忆受损,这凸显了它们作为潜在治疗靶点的重要性。最近关于线索性恐惧条件反射模型的研究阐明了参与恐惧记忆处理的神经回路。然而,关于多巴胺的作用以及多巴胺D2受体(D2R)拮抗剂的影响,已有相互矛盾的报道。关于慢性D2R拮抗剂治疗的临床效用,目前的知识明显有限。本研究旨在揭示此类治疗如何影响恐惧记忆处理。
我们使用线索性恐惧条件反射大鼠模型,并进行了为期14天的慢性氟哌啶醇治疗。随后,为了研究慢性氟哌啶醇治疗对恐惧条件性记忆表达和消退的影响,我们在暴露于条件刺激下观察了14天的僵住行为。
慢性氟哌啶醇治疗抑制了恐惧记忆表达时的僵住时间。相比之下,单次给予氟哌啶醇会增加恐惧记忆表达时的僵住时间并延迟消退。
本研究结果表明,抗精神病药物的慢性给药对恐惧记忆处理的影响与单剂量给药不同。这表明慢性D2R拮抗剂治疗的效果与药物的非特异性作用不同。本研究提供了基本见解,可能有助于我们未来理解与D2R相关的恐惧记忆障碍的治疗机制。