Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts.
Eur Arch Psychiatry Clin Neurosci
; 274(2): 445-452, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-37507486
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Globo Pálido
/
Trastornos Relacionados con Opioides
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Eur Arch Psychiatry Clin Neurosci
Asunto de la revista:
NEUROLOGIA
/
PSIQUIATRIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania