Journal article
Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts
European archives of psychiatry and clinical neuroscience, Vol.276(1), pp.339-348
02/2026
DOI: 10.1007/s00406-025-02139-0
PMCID: PMC12904868
PMID: 41205075
Abstract
Opioid addiction is a global concern and the largest health burden among drug use disorders. Prefrontal cortex (PFC) regions play a key multifaceted role in behavioural regulation, and GABAergic interneurons regulate the output of the PFC, whose dysfunction has been linked to the behavioural abnormalities observed in opioid-addicted individuals. In these neurons, glutamate decarboxylase (GAD), with its isoforms GAD 65 and 67, is a key enzyme in the synthesis of GABA. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the PFC regions, i.e. the anterior cingulate cortex (ACC), the orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC), in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil bilaterally. The neuropil was assessed in parallel with the density of immunostained somata. The study showed a significantly decreased neuropil density in layer III of the left ventral part of the ACC (ACCv) in 13 heroin-addicted males, compared to 12 healthy controls (U-test P value 0.04). There were no significant differences in somata density in any of the investigated PFC regions. Analysis of the confounding variables that differed significantly between the compared groups (i.e. age, brain volume, and duration of formalin fixation) showed that these variables did not affect the results. Our findings are the first in human postmortem research to suggest a dysregulation of the GABAergic system in the PFC region in opioid-addicted individuals, which supports human neuroimaging research and contributes to the understanding of opioid addiction.
Details
- Title: Subtitle
- Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts
- Creators
- Apollonia von Gilsa - Otto-von-Guericke-Universität MagdeburgJohann Steiner - German Center for Mental Health (DZPG), Partner Site Halle-Jena-Magdeburg, Magdeburg, GermanyAnna Gos - University Hospital of ZurichKurt Trübner - University of Duisburg-EssenChristian Mawrin - Otto-von-Guericke-Universität MagdeburgMichał Kaliszan - Gdańsk Medical UniversityThomas Nickl-Jockschat - German Center for Mental Health (DZPG), Partner Site Halle-Jena-Magdeburg, Magdeburg, GermanyTomasz Gos - Otto-von-Guericke-Universität Magdeburg
- Resource Type
- Journal article
- Publication Details
- European archives of psychiatry and clinical neuroscience, Vol.276(1), pp.339-348
- DOI
- 10.1007/s00406-025-02139-0
- PMID
- 41205075
- PMCID
- PMC12904868
- NLM abbreviation
- Eur Arch Psychiatry Clin Neurosci
- ISSN
- 1433-8491
- eISSN
- 1433-8491
- Publisher
- Springer Nature
- Grant note
- Alfried Krupp von Bohlen und Halbach-Stiftung / Alfried Krupp von Bohlen und Halbach-Stiftung 07R-1832 / Stanley Medical Research Institute BMBF NBL-3/2 and 01ZZ0407 / Bundesministerium für Bildung und Forschung XN3594O/0405M, N2-OVGU / Ministerium für Wissenschaft und Wirtschaft, Land Sachsen-Anhalt
- Language
- English
- Electronic publication date
- 11/08/2025
- Date published
- 02/2026
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9985024251402771
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