title: An evaluation of neuroplasticity and behavior after deep brain stimulation of the nucleus accumbens in an animal model of depression.
abstract: BACKGROUND
  Recent interest has demonstrated the nucleus accumbens (NAcc) as a potential target for the treatment of depression with deep brain stimulation (DBS).
  
  
  OBJECTIVE
  To demonstrate that DBS of the NAcc is an effective treatment modality for depression and that chemical and structural changes associated with these behavioral changes are markers of neuroplasticity.
  
  
  METHODS
  A deep brain stimulator was placed in the NAcc of male Wistar-Kyoto rats. Groups were divided into sham (no stimulation), intermittent (3 h/d for 2 weeks), or continuous (constant stimulation for 2 weeks). Exploratory and anxietylike behaviors were evaluated with the open-field test before and after stimulation. Tissue samples of the prefrontal cortex (PFC) were processed with Western blot analysis of markers of noradrenergic activity that included the noradrenergic synthesizing enzyme tyrosine hydroxylase. Analysis of tissue levels for catecholamines was achieved with high-performance liquid chromatography. Morphological properties of cortical pyramidal neurons were assessed with Golgi-Cox staining.
  
  
  RESULTS
  Subjects undergoing intermittent and continuous stimulation of the NAcc exhibited an increase in exploratory behavior and reduced anxietylike behaviors. Tyrosine hydroxylase expression levels were decreased in the PFC after intermittent and continuous DBS, and dopamine and norepinephrine levels were decreased after continuous stimulation. Golgi-Cox staining indicated that DBS increased the length of apical and basilar dendrites in pyramidal neurons of the PFC.
  
  
  CONCLUSIONS
  Deep brain stimulation induces behavioral improvement in and neurochemical and morphological alterations of the PFC that demonstrate changes within the circuitry of the brain different from the target area of stimulation. This observed dendritic plasticity may underlie the therapeutic efficacy of this treatment.
authors.affiliation: Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. sfalowski@gmail.com
authors.forename: Steven M
authors.initials: SM
authors.lastname: Falowski
authors.forename: Ashwini
authors.initials: A
authors.lastname: Sharan
authors.forename: Beverly A S
authors.initials: BA
authors.lastname: Reyes
authors.forename: Carl
authors.initials: C
authors.lastname: Sikkema
authors.forename: Patricia
authors.initials: P
authors.lastname: Szot
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Van Bockstaele
mesh_terms: D000818:Animals; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D046690:Deep Brain Stimulation / Q000379:methods*; D003863:Depression / Q000473:pathology / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000503:physiopathology / Q000648:ultrastructure; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D016622:Silver Staining; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050482:Catecholamine Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase