Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people

Arch Gen Psychiatry. 2008 Apr;65(4):466-75. doi: 10.1001/archpsyc.65.4.466.


Context: Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence.

Objective: To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation.

Design: Functional brain imaging was conducted during alcohol cue presentation.

Setting: Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute.

Patients: Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (< 14 drinks per week) paid volunteers recruited through advertisements at an academic center.

Interventions: A taste of alcohol and a series of alcohol-related pictures, neutral beverage pictures, and visual control images were provided to volunteers after 7 days of double-blind randomly assigned daily dosing with 50 mg of naltrexone (n = 23), 0.50 mg of ondansetron hydrochloride (n = 23), the combination of the 2 medications (n = 20), or matching placebos (n = 24).

Main outcome measures: Difference in brain blood oxygen level-dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving.

Results: The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue-induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis.

Conclusions: Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alcoholism / physiopathology*
  • Alcoholism / rehabilitation*
  • Basal Ganglia / blood supply
  • Basal Ganglia / metabolism*
  • Cerebrovascular Circulation
  • Cues
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Naltrexone / therapeutic use*
  • Narcotics / therapeutic use*
  • Ondansetron / therapeutic use*
  • Oxygen / metabolism
  • Photic Stimulation
  • Serotonin Antagonists / therapeutic use*
  • Severity of Illness Index


  • Narcotics
  • Serotonin Antagonists
  • Ondansetron
  • Naltrexone
  • Oxygen