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Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts.
- Source :
-
European archives of psychiatry and clinical neuroscience [Eur Arch Psychiatry Clin Neurosci] 2024 Mar; Vol. 274 (2), pp. 445-452. Date of Electronic Publication: 2023 Jul 28. - Publication Year :
- 2024
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Abstract
- 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.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1433-8491
- Volume :
- 274
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European archives of psychiatry and clinical neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 37507486
- Full Text :
- https://doi.org/10.1007/s00406-023-01656-0