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

Abstract

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.

Figures

Figure 1

Subjective craving for alcohol and beverage cues were rated within the scanner. Subjects treated with the combination of naltrexone/ondansetron had significantly less craving for alcohol as compared to placebo-treated subjects (p=.035). In addition, social drinking controls had less craving for alcohol as compared to placebo-treated subjects (p=.001).

Figure 2

Brain regions with significantly increased activation in one task (alcohol) compared with another (beverage) are depicted in color on coronal structural magnetic resonance imaging scans (p ≤.001).

Figure 3

Ventral striatum activation (contrast of alcohol-cue activation minus beverage-cue activation) was significantly decreased in the combination naltrexone/ondansetron group (p=.02), the naltrexone alone (p=.049), and the social drinking controls (p=.001) as compared to placebo treated subjects.

Figure 4

There is a strong curvolinear relationship across groups between the mean craving for alcohol during the scanning session and the mean of the alcohol minus beverage comparison (B=.04, Se=.0048, p= 002) in the ventral striatum.