Impairment of the GABAergic system in the anterior midcingulate cortex of heroin-addicted males.

Abstract

Opioid addiction is a global concern and the largest health burden among drug use disorders. The multifunctional anterior midcingulate cortex (aMCC) is critical for processing nociceptive input and negative emotions, which play a prominent role in the maintenance of opioid addiction. GABAergic interneurons regulate the output of the aMCC, whose dysfunction has been linked to the behavioural abnormalities observed in addiction. In these neurons, glutamate decarboxylase (GAD), with its isoforms GAD 65 and 67, is a key enzyme in the synthesis of GABA. However, there is a lack of research investigating the role of the GABAergic system in the aMCC in the context of 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 aMCC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. Assessment of neuropil was performed in parallel with assessment of density of immunostained somata. The study showed decreased neuropil density in layers III and V in the left MCC of 13 heroin-addicted males compared to 12 healthy controls, with a significant U-test P value for layer V. In contrast, the density of GAD-immunostained somata was increased bilaterally in MCC layers III and V, but not significantly. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings are the first to suggest a dysregulation of GABAergic system in the aMCC in opioid-addicted individuals, contributing to the understanding of opioid addiction.