Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment and Prediction of Relapse to Heavy Drinking

Abstract

Background and Aims: Baclofen, a GABA_B agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial. Methods: Participants included 31 alcohol dependent individuals (recent drinking: N = 16; and abstinent: N = 15) who had received daily baclofen (BAC 30-75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using in vivo proton magnetic resonance spectroscopy (¹H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC. Results: When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH (p < 0.01) and NAA (p < 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: F = 14.28, R² = 0.85; GSH: B = -1.22, p = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: F = 6.50, R² = 0.72; GSH: B = 0.99, p = 0.06). Conclusion: Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder.

Keywords: GABA; GSH; NAA; alcohol dependence; baclofen; glutamate.

Figure 1

T1-weighted structural image showing the anatomical localization of 3 × 3 × 3 acquisition voxel.

Figure 2

Example MR-spectrum from the right parietal cortex.

Figure 3

(A) GSH/Cr and (B) NAA/Cr in the right parietal cortex for PL (placebo) and BAC (baclofen: 30–75 mg) treated alcohol dependent patients (•, recent alcohol consumption <24 h; °, no recent alcohol consumption <24 h).