Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens

作     者：MAYu CHEN Ning WANG Hui-min Meng Fan-gang ZHANG Jian-guo 

作者机构：Department of Functional Neurosurgery Beijing NeurosurgicalInstitute Capital Medical University Beijing 100050 China Department of Neurosurgery Beijing Tiantan Hospital CapitalMedical University Beijing 100050 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2013年第126卷第10期

页      面：1939-1943页

核心收录：

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：This work was supported by grants from the National Natural Science Foundation of China （No. 81070901  No. 81141013）  the Beijing Outstanding Talents Project （No. 2011 D003034000019）  and Beijing Nova Program （No. 2008B043）. 

主　　题：stimulation, nucleus accumbens morphine, drug dependency 

摘      要：Background Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens （NAc） in addiction. Deep brain stimulation （DBS） has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats. Methods A morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance （ANOVA） followed by Tukey＇s tests for multiple post hoc comparisons. Results High-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS （（268.25±25.07） seconds） was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration （（303.29±34.22） seconds）. High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory. Conclusion Bilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction.