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Intra-nucleus accumbens shell injection of baclofen blocks the reconsolidation of conditioned place preference in morphine-addicted mice

WANG Ruo-Chen¹, XIAO Li-Fei^1,2, ZHANG Chun^1,2, SUN Tao^1,2,3, SUN Kui-Sheng^1,2,3,*

¹School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China；²Ningxia Key Laboratory of Cerebrocranial Diseases, Yinchuan 750004, China;；³Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan 750001, China

Abstract

Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABAB receptor agonist, is the only specific GABAB receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABAB receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABAB receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.

Key words: morphine addiction; memory reconsolidation; conditioned place preference; nucleus accumbens shell; baclofen

Received: 2019-05-05　　Accepted: 2019-11-26

Corresponding author: 孙奎胜　　E-mail: sunkuisheng79@163.com

DOI: 10.13294/j.aps.2020.0001

Citing This Article：

WANG Ruo-Chen, XIAO Li-Fei, ZHANG Chun, SUN Tao, SUN Kui-Sheng. Intra-nucleus accumbens shell injection of baclofen blocks the reconsolidation of conditioned place preference in morphine-addicted mice. Acta Physiol Sin 2020; 72 (2): 255-261 (in Chinese with English abstract).