Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Rationale</jats:title><jats:p>One hallmark of addiction is an altered neuronal reward processing. In healthy individuals (HC), reduced activity in fronto-striatal regions including the insula has been observed when a reward anticipation task was performed repeatedly. This effect could indicate a desensitization of the neural reward system due to repetition. Here, we investigated this hypothesis in a cohort of patients with alcohol use disorder (AUD), who have been treated with baclofen or a placebo. The efficacy of baclofen in AUD patients has been shown to have positive clinical effects, possibly via indirectly affecting structures within the neuronal reward system.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>Twenty-eight recently detoxified patients (13 receiving baclofen (BAC), 15 receiving placebo (PLA)) were investigated within a longitudinal, double-blind, and randomized pharmaco-fMRI design with an individually adjusted daily dosage of 30–270 mg.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Brain responses were captured by functional magnetic resonance imaging (fMRI) during reward anticipation while participating in a slot machine paradigm before (t1) and after 2 weeks of individual high-dose medication (t2).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Abstinence rates were significantly higher in the BAC compared to the PLA group during the 12-week high-dose medication phase. At t1, all patients showed significant bilateral striatal activation. At t2, the BAC group showed a significant decrease in insular activation compared to the PLA group.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>By affecting insular information processing, baclofen might enable a more flexible neuronal adaptation during recurrent reward anticipation, which could resemble a desensitization as previously observed in HC. This result strengthens the modulation of the reward system as a potential mechanism of action of baclofen.</jats:p></jats:sec><jats:sec><jats:title>Trial registration</jats:title><jats:p>Identifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665.</jats:p></jats:sec>