TY - JOUR
T1 - Neurodegeneration of lateral habenula efferent fibers after intermittent cocaine administration
T2 - Implications for deep brain stimulation
AU - Lax, Elad
AU - Friedman, Alexander
AU - Croitoru, Ofri
AU - Sudai, Einav
AU - Ben-Moshe, Hila
AU - Redlus, Lior
AU - Sasson, Efrat
AU - Blumenfeld-Katzir, Tamar
AU - Assaf, Yaniv
AU - Yadid, Gal
N1 - 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.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Cocaine addiction
KW - Deep brain stimulation
KW - Diffusion tensor imaging
KW - Lateral habenula
KW - Magnetic resonance imaging
KW - Neurodegeneration
KW - Retrograde labeling
UR - http://www.scopus.com/inward/record.url?scp=84883799361&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2013.06.034
DO - 10.1016/j.neuropharm.2013.06.034
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C2 - 23891640
AN - SCOPUS:84883799361
SN - 0028-3908
VL - 75
SP - 246
EP - 254
JO - Neuropharmacology
JF - Neuropharmacology
ER -