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

Author:

Enomoto Kosuke1,Shibata Kazuro1ORCID,Muraoka Hiroyuki2,Kawano Masahiko3,Inada Ken2ORCID,Ishigooka Jun4,Nishimura Katsuji1ORCID,Oshibuchi Hidehiro1ORCID

Affiliation:

1. Department of Psychiatry Tokyo Women's Medical University Tokyo Japan

2. Department of Psychiatry Kitasato University Sagamihara‐shi Kanagawa Japan

3. Miyakonojo‐Shinsei Hospital Miyazaki Japan

4. CNS Pharmacological Research Institute Tokyo Japan

Abstract

AbstractAimImpairments 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.MethodsWe 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.ResultsChronic 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.ConclusionThe 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.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

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