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


METHODS
Functional brain imaging was conducted during alcohol cue presentation.


METHODS
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.


METHODS
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.


METHODS
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).


METHODS
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.
Myrick
Hugh
H
Research and Development Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA. myrickh@musc.edu
Anton
Raymond F
RF
Li
Xingbao
X
Henderson
Scott
S
Randall
Patrick K
PK
Voronin
Konstantin
K
D000328:Adult; D000437:Alcoholism / Q000503:physiopathology* / Q000534:rehabilitation*; D001479:Basal Ganglia / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D003463:Cues; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use*; D009294:Narcotics / Q000627:therapeutic use*; D017294:Ondansetron / Q000627:therapeutic use*; D010100:Oxygen / Q000378:metabolism; D010775:Photic Stimulation; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D012720:Severity of Illness Index
D009294:Narcotics; D012702:Serotonin Antagonists; D017294:Ondansetron; D009271:Naltrexone; D010100:Oxygen