Imaging of Microtubules in a Nonhuman Primate Model of Alcohol Use Disorder

Microtubules (MTs), as structural components of the cytoskeleton, are vital for axonal transport, information processing, and signaling within the brain. Disruption of MT integrity has been associated with neurological disorders, including alcohol use disorder (AUD). This study used positron emission tomography (PET) imaging with the radiotracer [¹¹C]MPC-6827 to investigate alcohol-induced changes in MT dynamics in a nonhuman primate model of AUD. Dynamic PET scans (0-120 min) were conducted in male cynomolgus monkeys (n = 4) before and after ∼7 months of ethanol self-administration (EtOH SA). Quantitative analysis of standardized uptake values and time-activity curves demonstrated a consistent decrease in [¹¹C]MPC-6827 uptake across multiple brain regions, particularly in the amygdala, globus pallidus, and substantia innominata. Statistically significant reductions in tracer uptake were observed in early scan windows (15 and 30 min), suggesting compromised MT integrity due to chronic EtOH SA. These findings provide compelling evidence that chronic alcohol consumption induces significant changes in microtubule dynamics, potentially contributing to pathological processes underlying AUD.