DBS of nucleus accumbens on heroin seeking behaviors in self-administering rats.
BACKGROUND
Surgical ablation of select brain areas has been frequently used to alleviate psychological dependence on opiate drugs in certain countries. However, ablative brain surgery was stopped in China in 2004 due to the related ethical controversy and possible side effects. Deep brain stimulation (DBS), a less invasive, reversible and adjustable process of neuromodulation, was adopted to attenuate relapses in studies of drug addiction.


METHODS
Preclinical experiments were designed to assess the long-term effects of DBS of the nucleus accumbens (NAc) on cue- and heroin-induced reinstatement of drug seeking behaviors. After a rat self-administration model of heroin relapse was established, DBS was administered bilaterally or unilaterally to the NAc core through concentric bipolar electrodes. A 1-h long continuous stimulation (130 Hz, 100 μs, 0-150 μA) was given daily for 7 days during the abstinence session. Drug seeking behaviors were elicited by conditioned cues or a small dose of heroin.


RESULTS
75 μA and 150 μA bilateral NAc DBS attenuated cue- and heroin-induced reinstatement of drug seeking, and unilateral DBS of the right NAc achieved effects almost equivalent to bilateral DBS. Additional experiments showed that DBS had no long-term influence on locomotor activity and spatial learning and retention capabilities in Morris water maze tasks. Subsequent immunohistochemistry measurements revealed that the behavioral consequences were associated with a significant increase in the expression of pCREB and a reduction in the expression of ΔFosB in the NAc.


CONCLUSIONS
These findings indicate that the NAc DBS could be an effective and safe therapeutic option for preventing relapse to heroin addiction.
Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
Liemei
L
Guo
Hongyu
H
Zhou
Ran
R
Wang
Jiwen
J
Xu
Wenhua
W
Zhou
Fuqiang
F
Zhang
Shuaien
S
Tang
Huifen
H
Liu
Jiyao
J
Jiang
D000818:Animals; D002404:Catheterization; D003216:Conditioning, Operant; D003463:Cues; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D004567:Electrodes, Implanted; D003932:Heroin / Q000494:pharmacology*; D006556:Heroin Dependence / Q000523:psychology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D017362:Cyclic AMP Response Element-Binding Protein; C483820:Fosb protein, rat; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D003932:Heroin