Intra-nucleus accumbens shell injection of baclofen blocks the reconsolidation of conditioned place preference in morphine-addicted mice.
- Author:
Ruo-Chen WANG
1
;
Li-Fei XIAO
1
;
Chun ZHANG
1
;
Tao SUN
1
;
Kui-Sheng SUN
1
Author Information
1. School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Baclofen;
administration & dosage;
Conditioning, Classical;
GABA-B Receptor Agonists;
administration & dosage;
Locomotion;
Male;
Memory;
Mice;
Mice, Inbred C57BL;
Morphine;
Nucleus Accumbens;
drug effects;
Opioid-Related Disorders;
Reward
- From:
Acta Physiologica Sinica
2020;72(2):255-261
- CountryChina
- Language:Chinese
-
Abstract:
Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA 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 GABA 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 GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.
