Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior

Alexander Friedman, Elad Lax, Yahav Dikshtein, Lital Abraham, Yakov Flaumenhaft, Einav Sudai, Moshe Ben-Tzion, Lavi Ami-Ad, Rami Yaka, Gal Yadid

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABAAβ, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalNeuropharmacology
Volume59
Issue number6
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
This study was supported by NIH (grant 1R21DA027776-01 ) to GY. AF and EL was supported by a President's Fellowship, Bar-Ilan University. The research reported in this article was completed as part of AF's Ph.D. dissertation.

Keywords

  • Addiction
  • Cocaine self-administration
  • Deep brain stimulation
  • Lateral habenula
  • Negative reward
  • Sucrose self-administration

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