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Neuropharmacology. 2013 Dec;75:246-54. doi: 10.1016/j.neuropharm.2013.06.034. Epub 2013 Jul 24.

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

Author information

1
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
2
The Leslie & Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel.
3
Department of Neurobiology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel.
4
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; The Leslie & Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel. Electronic address: yadidg@mail.biu.ac.il.

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.

KEYWORDS:

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

[Indexed for MEDLINE]

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