Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts

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.