title: Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum.
abstract: Recent research in humans and rodents has explored the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VS) as a possible treatment for drug addiction. However, the optimum electrode placement and optimum DBS parameters have not been thoroughly studied. Here we varied stimulation sites and frequencies to determine whether DBS of the VS could facilitate the extinction of morphine-induced conditioned place preference in rats.
  
  
  
  Rats were implanted with DBS electrodes in the dorsal or ventral subregions of the VS and trained to the morphine conditioned place preference. Subsequently, rats received extinction sessions over 9 days, combined with 60 min of either high- (130 Hz) or low- (20 Hz) frequency DBS. To study circuit-wide activations after DBS of the VS, c-fos immunohistochemistry was performed in regions involved in the extinction of drug-seeking behaviors.
  
  
  
  High-frequency DBS of the dorsal-VS impaired both extinction training and extinction memory, whereas high-frequency DBS of the ventral-VS had no effect. In contrast, low-frequency DBS of the dorsal-VS strengthened extinction memory when tested 2 or 9 days after the cessation of stimulation. Both DBS frequencies increased c-fos expression in the infralimbic prefrontal cortex, but only low-frequency DBS increased c-fos expression in the basal amygdala and the medial portion of the central amygdala.
  
  
  
  Our results suggest that low-frequency (rather than high-frequency) DBS of the dorsal-VS strengthens extinction memory and may be a potential adjunct for extinction-based therapies for treatment-refractory opioid addiction.
authors.affiliation: Department of Anatomy and Neurobiology, San Juan, Puerto Rico.
authors.forename: Freddyson J
authors.initials: FJ
authors.lastname: Martínez-Rivera
authors.affiliation: Department of Psychiatry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez-Romaguera
authors.affiliation: Department of Anatomy and Neurobiology, San Juan, Puerto Rico.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lloret-Torres
authors.affiliation: Department of Psychiatry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Fabricio H
authors.initials: FH
authors.lastname: Do Monte
authors.affiliation: Department of Anatomy and Neurobiology, San Juan, Puerto Rico; Department of Psychiatry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Quirk
authors.affiliation: Department of Anatomy and Neurobiology, San Juan, Puerto Rico; Department of Psychiatry, School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico. Electronic address: jennifer.barreto1@upr.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Barreto-Estrada
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D066328:Ventral Striatum / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine
keywords: Amygdala; CPP; DBS; Extinction; Morphine; Ventral striatum