title: Chronic unilateral stimulation of the nucleus accumbens at high or low frequencies attenuates relapse to cocaine seeking in an animal model.
abstract: BACKGROUND
  Deep brain stimulation (DBS), a form of neurosurgical intervention that is used to modulate the electrophysiological activity of specific brain areas, has emerged as a form of therapy for severe cases of treatment-refractory addiction.
  
  
  OBJECTIVE
  Recent research suggests that the nucleus accumbens (NAC) is a promising target area for DBS in addiction. The current experiments were designed to determine optimal parameters of stimulation and long-term efficacy of NAC DBS in an animal model of cocaine addiction.
  
  
  METHODS
  Rats were implanted with a stimulating electrode in the right NAC and exposed to chronic cocaine self-administration (0.5 mg/kg/infusion). Rats underwent drug seeking tests by exposing them to the self-administration context paired with cocaine challenge (5 mg/kg i.p.) on days 1, 15 and 30 after withdrawal from cocaine self-administration. Low-frequency (LF, 20 Hz) or high-frequency (HF, 160 Hz) DBS was applied for 30 min daily for 14 consecutive days starting one day after drug withdrawal.
  
  
  RESULTS
  Rats exhibited robust drug-seeking 1, 15 and 30 days after withdrawal from cocaine self-administration, with responding being highest on day 15. Both LF and HF attenuated cocaine seeking on day 15 post-withdrawal by 36 and 48%, respectively. Both forms of stimulation were ineffective on the tests conducted on days 1 and 30.
  
  
  CONCLUSIONS
  The present data showed that unilateral DBS of the NAC effectively attenuated cocaine relapse after 15 days of drug withdrawal, with therapeutic-like effects seemingly diminishing after DBS discontinuation. This evidence provides support for DBS as a promising intervention in intractable cases of stimulant addiction.
authors.affiliation: Department of Psychology, University of Canterbury, Christchurch, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Hamilton
authors.affiliation: Department of Psychology, University of Canterbury, Christchurch, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: School of Psychology, University of Leicester, Leicester, United Kingdom. Electronic address: juan.canales@uv.es.
authors.forename: J J
authors.initials: JJ
authors.lastname: Canales
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000517:prevention & control / Q000628:therapy*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D012008:Recurrence; D012055:Reinforcement Schedule; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration
chemical_list: D012439:Saccharin; D003042:Cocaine
keywords: Addiction; Cocaine; Deep brain stimulation; Nucleus accumbens; Relapse