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An Evaluation of Neuroplasticity and Behavior After Deep Brain Stimulation of the Nucleus Accumbens in an Animal Model of Depression

Falowski, Steven M. MD*; Sharan, Ashwini MD*; Reyes, Beverly A. S. DVM, PhD; Sikkema, Carl BS§; Szot, Patricia PhD§; Van Bockstaele, Elisabeth J. PhD

doi: 10.1227/NEU.0b013e3182237346

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.

CONCLUSION: 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.

*Department of Neurosurgery and

Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, Pennsylvania

§MIRECC, VA Puget Sound Health Care System, Seattle, Washington

Correspondence: Steven M. Falowski, MD, Department of Neurosurgery, Thomas Jefferson University, 909 Walnut St, Philadelphia, PA 19107. E-mail:

Received November 17, 2010

Accepted April 5, 2011

Copyright © by the Congress of Neurological Surgeons