1. Impairment of the GABAergic system in the anterior insular cortex of heroin-addicted males.
- Author
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Gos A, Steiner J, Trübner K, Mawrin C, Kaliszan M, and Gos T
- Subjects
- Male, Humans, Adult, Middle Aged, gamma-Aminobutyric Acid metabolism, Young Adult, Glutamate Decarboxylase metabolism, Heroin Dependence metabolism, Heroin Dependence pathology, Insular Cortex metabolism, Insular Cortex diagnostic imaging, Insular Cortex pathology
- Abstract
Opioid addiction is a global problem, causing the greatest health burden among drug use disorders, with opioid overdose deaths topping the statistics of fatal overdoses. The multifunctional anterior insular cortex (AIC) is involved in inhibitory control, which is severely impaired in opioid addiction. GABAergic interneurons shape the output of the AIC, where abnormalities have been reported in individuals addicted to opioids. In these neurons, glutamate decarboxylase (GAD) with its isoforms GAD 65 and 67 is a key enzyme in the synthesis of GABA, and research data point to a dysregulation of GABAergic activity in the AIC in opioid addiction. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the AIC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. The study showed bilaterally increased neuropil density in layers III and V in 13 male heroin-addicted males compared to 12 healthy controls, with significant U-test P values for layer V bilaterally. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings suggest a dysregulation of GABAergic activity in the AIC in opioid addiction, which is consistent with experimental data from animal models and human neuroimaging studies., Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Ethical approval: The study has been approved by the local ethics committee of the University of Magdeburg as performed in accordance with the ethical standards laid down in the Declaration of Helsinki of 1989. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)
- Published
- 2025
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