Effects of baclofen on insular gain anticipation in alcohol-dependent patients — a randomized, placebo-controlled, pharmaco-fMRI pilot trial.
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| Title: | Effects of baclofen on insular gain anticipation in alcohol-dependent patients — a randomized, placebo-controlled, pharmaco-fMRI pilot trial. |
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| Authors: | Pelz, Patricia, Genauck, Alexander, Lorenz, Robert C., Wüstenberg, Torsten, Wackerhagen, Carolin, Charlet, Katrin, Gleich, Tobias, Geisel, Olga, Heinz, Andreas, Müller, Christian A., Beck, Anne |
| Source: | Psychopharmacology. Jan2023, Vol. 240 Issue 1, p171-183. 13p. 2 Diagrams, 2 Charts, 1 Graph. |
| Subjects: | Baclofen, Alcoholism, Functional magnetic resonance imaging, Insular cortex, Reward (Psychology), Detoxification (Substance abuse treatment) |
| Abstract: | Rationale: 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. Objectives: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: Identifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Rationale: 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. Objectives: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: Identifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00333158 |
| DOI: | 10.1007/s00213-022-06291-6 |
