Neurodegeneration of lateral habenula efferent fibers after intermittent cocaine administration: Implications for deep brain stimulation

Elad Lax, Alexander Friedman, Ofri Croitoru, Einav Sudai, Hila Ben-Moshe, Lior Redlus, Efrat Sasson, Tamar Blumenfeld-Katzir, Yaniv Assaf, Gal Yadid*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Deep brain stimulation (DBS) is an emerging technique for effective, non-pharmacological intervention in the course of neurological and neuropsychiatric diseases. Several brain targets have been suggested as suitable for DBS treatment of drug addiction. Previously, we showed that DBS of the lateral habenula (LHb) can reduce cocaine intake, facilitate extinction and attenuate drug-induced relapse in rats trained to self-administrate cocaine. Herein, we demonstrated that cocaine self-administration dose-dependently decreased connectivity between the LHb and midbrain, as shown by neurodegeneration of the main LHb efferent fiber, the fasciculus retroflexus (FR). FR degeneration, in turn, may have caused lack of response to LHb stimulation in rats trained to self-administer high-dose cocaine (1.5 mg/kg; i.v.). Furthermore, we show that the micro-structural changes caused by cocaine can be non-invasively detected using magnetic resonance imaging and diffusion tensor imaging. Detection of cocaine-induced alterations in FR anatomy can aid the selection of potential responders to LHb stimulation for treatment of drug addiction.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
StatePublished - 2013


FundersFunder number
Israel Anti-Drug Authority
Wolf Foundation, Israel
National Institutes of Health
National Institute on Drug AbuseR21DA027776
Bar-Ilan University


    • Cocaine addiction
    • Deep brain stimulation
    • Diffusion tensor imaging
    • Lateral habenula
    • Magnetic resonance imaging
    • Neurodegeneration
    • Retrograde labeling


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