Disrupting Heroin-associated Memory Reconsolidation Through Actin Polymerization Inhibition in the Nucleus Accumbens Core

Overview

Journal Int J Neuropsychopharmacol

Publisher Oxford University Press

Specialty Psychiatry

Date 2024 Dec 24

PMID 39716383

Authors

Haiting Zhao

Haoyu Li

Li Meng

Peng Du

Xin Mo

Mengqi Gong

Jiaxin Chen

Yiwei Liao

Affiliations

Soon will be listed here.

Abstract

Background: Understanding drug addiction as a disorder of maladaptive learning, where drug-associated or environmental cues trigger drug cravings and seeking, is crucial for developing effective treatments. Actin polymerization, a biochemical process, plays a crucial role in drug-related memory formation, particularly evident in conditioned place preference paradigms involving drugs like morphine and methamphetamine. However, the role of actin polymerization in the reconsolidation of heroin-associated memories remains understudied.

Methods: This study employed a rodent model of self-administered heroin to investigate the involvement of actin polymerization in the reconsolidation of heroin-associated memories. Rats underwent ten days of intravenous heroin self-administration paired with conditioned cues. Subsequently, a 10-day extinction phase aimed to reduce heroin-seeking behaviors. Following this, rats participated in a 15-minute retrieval trial with or without cues. Immediately post-retrieval, rats received bilateral injections of the actin polymerization inhibitor Latrunculin A (Lat A) into the nucleus accumbens core (NACc), a critical brain region for memory reconsolidation.

Results: Immediate administration of Lat A into the NACc post-retrieval significantly reduced cue-induced and heroin-primed reinstatement of heroin-seeking behavior for at least 28 days. However, administering Lat A 6-hour post-retrieval or without a retrieval trial, as well as administering Jasplakionlide prior to memory reactivation did not affect heroin-seeking behaviors.

Conclusions: Inhibiting actin polymerization during the reconsolidation window disrupts heroin-associated memory reconsolidation, leading to decreased heroin-seeking behavior and prevention of relapse. These effects are contingent upon the presence of a retrieval trial and exhibit temporal specificity, shedding light on addiction mechanisms and potential therapeutic interventions.

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