Abstract
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 language | English |
|---|---|
| Pages (from-to) | 246-254 |
| Number of pages | 9 |
| Journal | Neuropharmacology |
| Volume | 75 |
| DOIs | |
| State | Published - 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.
Funding
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.
| Funders | Funder number |
|---|---|
| Israel Anti-Drug Authority | |
| Wolf Foundation, Israel | |
| National Institutes of Health | |
| National Institute on Drug Abuse | R21DA027776 |
| Bar-Ilan University |
Keywords
- Cocaine addiction
- Deep brain stimulation
- Diffusion tensor imaging
- Lateral habenula
- Magnetic resonance imaging
- Neurodegeneration
- Retrograde labeling
