title: Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Fan-Gang
authors.initials: FG
authors.lastname: Meng
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D008297:Male; D009020:Morphine / Q000633:toxicity*; D009021:Morphine Dependence / Q000628:therapy*; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009020:Morphine