Post-retrieval Extinction Prevents Reconsolidation of Methamphetamine Memory Traces and Subsequent Reinstatement of Methamphetamine Seeking.

Ya-Yun Chen,Li-Bo Zhang,Yan-Xue Xue,Lin Lu,Jie Shi,Yi-Miao Gong,Yue Li,Shi-Qiu Meng

doi:10.3389/fnmol.2019.00157

Ya-Yun Chen, Li-Bo Zhang + Show 6 more

Open Access

https://doi.org/10.3389/fnmol.2019.00157

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Abstract

Methamphetamine abuse has become a serious public health problem. However, effective treatment for methamphetamine addiction remains elusive, especially considering its high rate of relapse after treatment. A conditioned stimulus (CS) memory retrieval–extinction procedure has been demonstrated to decrease reinstatement of cocaine, heroin, and alcohol seeking in rats, and to reduce cue-induced cravings in heroin and nicotine addicts. The goal of the present study is to explore the effect of the CS memory retrieval–extinction procedure on methamphetamine seeking in rats and the underlying mechanisms. We found that daily retrieval of methamphetamine-associated memories 1 h before extinction sessions decreased subsequent drug priming-induced reinstatement, spontaneous recovery, and renewal of methamphetamine seeking. We also found that retrieval of methamphetamine-associated memories induced neuronal activation in the basolateral amygdala (BLA), while presenting extinction within the time window of reconsolidation abolished the neuronal activation in BLA. These results indicate that the CS memory retrieval–extinction procedure could prevent reconsolidation of methamphetamine memory traces in BLA and subsequent methamphetamine craving and relapse.

Highlights

Methamphetamine addiction remains a significant public health concern worldwide, leading to devastating personal and social consequences
These results indicated that exposing rats to the conditioned stimulus (CS) retrieval manipulations 1 h but not 6 h before the extinction sessions attenuated methamphetamine-priming-induced reinstatement of methamphetamine seeking
We further demonstrated the effect of the CS memory retrieval–extinction procedure on renewal of methamphetamine seeking under a modified ABA renewal procedure based on previous studies (Xue et al, 2012; Luo et al, 2015), with two counterbalanced contexts: context A had stainless steel rod floor and gray walls, while context B had granular flat floor and walls covered in wallpaper with black and white patterns

Summary

Introduction

Methamphetamine addiction remains a significant public health concern worldwide, leading to devastating personal and social consequences. Frequent use of methamphetamine has been associated with severe neurotoxic effects and neurocognitive impairment (Ernst et al, 2000; Berman et al, 2008; Hart et al, 2012; Dean et al, 2013). There has been no medication approved by the FDA for the treatment of methamphetamine addiction so far. Psychosocial interventions, such as cognitive behavioral therapy, are considered to be cost- and time-intensive and with relatively poor outcomes given the high rates of relapse among methamphetamine addicts (Rawson et al, 2004; Shearer, 2007). It is of great importance to develop more effective interventions to treat methamphetamine addiction and to prevent relapse.

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