Radixin in the nucleus accumbens core modulates amphetamine-induced locomotor activity based on context association.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-06-03 DOI:10.1007/s00213-025-06823-w

Wen Ting Cai, Myung Ji Kwak, Joonyeup Han, Haeun Rim, Lars Björn Riecken, Helen Morrison, Wha Young Kim, Jeong-Hoon Kim

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引用次数: 0

Abstract

Rationale: The expression of addictive behaviors is linked to the structural plasticity of dendritic spines in the nucleus accumbens (NAcc). While radixin is known to contribute to morphological changes in dendritic spines, its role in the NAcc, specifically in the structural plasticity of dendritic spines and related drug-induced behavioral changes, is not well understood.

Objective: In the present study, we investigated the effects of radixin manipulation in the NAcc core on amphetamine (AMPH)-induced locomotor activity, both in association with and independent of a specific environment. Additionally, we examined the accompanying changes in dendritic spine density in this region.

Methods: We used a phosphomimetic pseudo-active mutant form (Rdx-T564D) and wild-type (Rdx-WT) radixin in conditioning and context-independent sensitization models induced by AMPH (1 mg/kg).

Results: We observed that Rdx-T564D in the NAcc core selectively inhibited the expression of non-associative locomotor sensitization induced by AMPH. Conversely, overexpression of Rdx-WT in this region inhibited both conditioned locomotor activity and context-specific locomotor sensitization. Spine analysis revealed that the increase in mature thin spine density observed in the context-paired group was specifically suppressed by Rdx-WT, but not by GFP or Rdx-T564D.

Conclusions: This study revealed that associative and non-associative forms of AMPH-induced reward memory are differentially regulated by radixin manipulation in the NAcc core, suggesting a critical role of radixin in psychomotor stimulant addiction.

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伏隔核核心的放射素调节安非他明诱导的基于情境关联的运动活动。

理论基础：成瘾行为的表达与伏隔核（NAcc）树突棘的结构可塑性有关。虽然已知radixin有助于树突棘的形态学改变，但其在NAcc中的作用，特别是在树突棘的结构可塑性和相关药物诱导的行为改变方面的作用，尚不清楚。目的：在本研究中，我们研究了放射素在NAcc核心的操作对安非他明（AMPH）诱导的运动活动的影响，包括与特定环境相关的和独立的。此外，我们还检查了该区域树突棘密度的伴随变化。方法：采用拟磷活性突变体（rx - t564d）和野生型（rx - wt）的雷达素，在AMPH诱导的条件作用和环境无关的致敏模型中（1 mg/kg）。结果：我们观察到NAcc核心Rdx-T564D选择性抑制AMPH诱导的非联合运动致敏的表达。相反，Rdx-WT在该区域的过度表达抑制了条件运动活动和情境特异性运动敏化。脊柱分析显示，在上下文配对组中观察到的成熟细棘密度的增加被Rdx-WT特异性抑制，而不是被GFP或Rdx-T564D抑制。结论：本研究揭示了在NAcc核心，桡心素操纵对amph诱导的联想和非联想形式的奖励记忆的不同调节，提示桡心素在精神运动兴奋剂成瘾中起着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.