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

Research output: Contribution to journalArticlepeer-review

17 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

Bibliographical note

Funding Information:
This study was supported by the NIH (grant # R21DA027776 ) to GY. EL was supported by a President's Fellowship, Bar-Ilan University, and fellowships from the Israel Anti-Drug Authority and the Wolf Foundation, Israel. The research reported in this article was completed as part of EL's Ph.D. dissertation. The authors wish to thank Michal Goldberg (Technion, Haifa, Israel) for her valuable contribution to the first stages of this research and to Dr. Tamar Sadan for critically reading and editing the manuscript.


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


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