Dynamic Changes of Cytoskeleton-Related Proteins Within Reward-Related Brain Regions in Morphine-Associated Memory.

Xixi Yang,Feifei Gao,Yichong Wen,Chunxia Yan,Zhuojin Yang,Jingsi Yang,Yuxiang Zhang

doi:10.3389/fnins.2020.626348

Xixi Yang, Feifei Gao + Show 5 more

Open Access

https://doi.org/10.3389/fnins.2020.626348

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Abstract

Drug-induced memory engages complex and dynamic processes and is coordinated at multiple reward-related brain regions. The spatiotemporal molecular mechanisms underlying different addiction phases remain unknown. We investigated the role of β-actin, as well as its potential modulatory protein activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) and extracellular signal-regulated kinase (ERK), in reward-related associative learning and memory using morphine-induced conditioned place preference (CPP) in mice. CPP was established by alternate morphine (10 mg/kg) injections and extinguished after a 10-day extinction training, while the withdrawal group failed to extinguish without training. In the nucleus accumbens (NAc), morphine enhanced the level of β-actin and Arc only during extinction, while p-ERK1/2 was increased during both CPP acquisition and extinction phases. In the dorsal hippocampus, morphine induced an upregulation of p-ERK only during extinction, while p-β-actin was elevated during both CPP establishment and extinction. In the dorsal hippocampus, Arc was elevated during CPP formation and suppressed during extinction. Compared with the NAc and dorsal hippocampus, dynamic changes in the medial prefrontal cortex (mPFC) and caudate putamen (CPu) were not very significant. These results suggested region-specific changes of p-β-actin, Arc/Arg3.1, and p-ERK1/2 protein during establishment and extinction phases of morphine-induced CPP. These findings unveiled a spatiotemporal molecular regulation in opiate-induced plasticity.

Highlights

Drug addiction is a brain disease, defined as compulsive drug use, and characterized by stubborn persistence despite adverse consequences (Hyman, 2005; Zhang et al, 2018)
Alterations of p-β-actin/β-actin Ratio, Arc Expression, and p-extracellular signal-regulated kinase (ERK)/ERK Ratio in the Nucleus Accumbens at Different Phases of Morphine-Induced Conditioned Place Preference Activation of striatal neurons critically contributes to drugassociated memories, so firstly, we examined the protein expression in nucleus accumbens (NAc)
The striatum, which was commonly divided into the dorsal part (CPu) and ventral part (NAc) based on anatomical localization, receives a prominent source of glutamatergic innervation from medial prefrontal cortex (mPFC) and hippocampus (Gonzales and Smith, 2015)

Summary

Introduction

Drug addiction is a brain disease, defined as compulsive drug use, and characterized by stubborn persistence despite adverse consequences (Hyman, 2005; Zhang et al, 2018). Long-term alterations in brain neural circuits are well known to be responsible for normal appetitive learning and memory processes (Torregrossa et al, 2011). Drug-associated memory is an aberrant memory that shares the Cytoskeletal-Associated Protein and Morphine Addiction same memory processes with other forms of memories (Liu et al, 2019). The striatum is a subcortical structure in the forebrain, which can be further subdivided into dorsal [caudate putamen (CPu)] and ventral [nucleus accumbens (NAc)], and is implicated in regulating responses to rewarding stimuli (Wang et al, 2019; Bang et al, 2020; Spechler et al, 2020). Exposure to addictive drugs has been shown to induce both structural and functional changes in these brain regions (Kai et al, 2018)

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