Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts

Anna Gos1, Johann Steiner1, Kurt Trübner2, Jonas Ungewickell1, Christian Mawrin3, Karol Karnecki4, Michał Kaliszan4, Tomasz Gos5,4
1Department of Psychiatry, Otto-von-Guericke University, Magdeburg, Germany
2Institute of Legal Medicine, University of Duisburg-Essen, Essen, Germany
3Department of Neuropathology, Otto-von-Guericke-University Magdeburg, Germany
4Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland
5Department of Psychiatry, Otto-von-Guericke-University, Magdeburg, Germany

Tóm tắt

Opioid addiction is a global problem that has been exacerbated in the USA and Europe by the COVID-19 pandemic. The globus pallidus (GP) plays a prominent neurobiological role in the regulation of behaviour as an output station of the striato-pallidal system. GABAergic large projection neurons are the main neuronal type in the external (EGP) and internal (IGP) parts of the GP, where addiction-specific molecular and functional abnormalities occur. In these neurons, glutamate decarboxylase (GAD) with isoforms GAD 65 and 67 is a key enzyme in GABA synthesis, and experimental studies suggest GAD dysregulation in the GP of heroin addicts. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of large GP neurons by densitometric evaluation of their GAD 65/67-immunostained thick dendrites. The study revealed a bilaterally decreased fibres density in the EGP paralleled by the increase in the IGP in 11 male heroin addicts versus 11 healthy controls (significant U-test P values). The analysis of confounding variables found no interference of age, brain volume, and duration of formalin fixation with the results. Our findings suggest a dysregulation of GABAergic activity in the GP of heroin addicts, which is consistent with experimental data from animal models and plays potentially a role in the disturbed function of basal ganglia circuit in opioid addiction.

Tài liệu tham khảo

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