title: High Frequency Electrical Stimulation of Lateral Habenula Reduces Voluntary Ethanol Consumption in Rats.
abstract: BACKGROUND
  Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanol-drinking behavior in rats.
  
  
  METHODS
  We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb.
  
  
  RESULTS
  c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior.
  
  
  CONCLUSIONS
  Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.forename: Rao
authors.initials: R
authors.lastname: Fu
authors.forename: Guiqin
authors.initials: G
authors.lastname: Xie
authors.forename: Amandeep
authors.initials: A
authors.lastname: Kaur
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
authors.forename: Jiang Hong
authors.initials: JH
authors.lastname: Ye
keywords: c-Fos immunohistochemistry; deep brain stimulation; drug abuse; locomotion