Effects of chronic haloperidol treatment on the expression of fear memory and fear memory extinction in the cued fear-conditioned rats.

IF 2 Q3 NEUROSCIENCES Neuropsychopharmacology Reports Pub Date : 2024-03-01 Epub Date: 2024-02-14 DOI:10.1002/npr2.12418
Kosuke Enomoto, Kazuro Shibata, Hiroyuki Muraoka, Masahiko Kawano, Ken Inada, Jun Ishigooka, Katsuji Nishimura, Hidehiro Oshibuchi
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Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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慢性氟哌啶醇治疗对诱导恐惧条件反射大鼠恐惧记忆表达和恐惧记忆消退的影响
目的:在多种精神疾病中经常可以观察到情绪记忆受损的现象,这凸显了情绪记忆作为潜在治疗靶点的重要性。最近对诱导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,关于多巴胺的作用和多巴胺 D2 受体(D2R)拮抗剂的影响,研究结果却相互矛盾。关于慢性 D2R 拮抗剂治疗的临床效用,人们的了解显然有限。本研究旨在揭示此类治疗如何影响恐惧记忆处理:方法:我们利用诱导恐惧条件反射大鼠模型,对其进行为期 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反射记忆表达和消退的影响,我们观察了大鼠在暴露于条件刺激14天后的冻结行为:结果:长期氟哌啶醇治疗抑制了恐惧记忆表达的冻结时间。结果:长期氟哌啶醇治疗抑制了恐惧记忆表达的凝固时间,而单次氟哌啶醇治疗则增强了恐惧记忆表达的凝固时间并延迟了消退:结论:本研究结果表明,长期服用抗精神病药物对恐惧记忆处理的影响与单剂量服用不同。这表明,慢性 D2R 拮抗剂治疗的影响不同于药物的非特异性影响。这项研究提供了基本的见解,可能有助于我们今后了解与D2R相关的恐惧记忆障碍的治疗机制。
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来源期刊
Neuropsychopharmacology Reports
Neuropsychopharmacology Reports Psychology-Clinical Psychology
CiteScore
3.60
自引率
4.00%
发文量
75
审稿时长
14 weeks
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