Striatal Signatures of Cocaine Addiction and Structural Neuroadaptations in the Basal Ganglia

Abstract

Cocaine addiction presents a complex challenge to neuroscience, combining behavioral compulsivity with strong neurobiological disruption. Among the brain regions most consistently implicated in the progression of this disease is the basal ganglia, a system of interconnected nuclei that plays a central role in motor control, reward learning, and the formation of habitual behaviors. While acute cocaine exposure to the basal ganglia primarily influences dopamine transmission, chronic use triggers broader neuroadaptations that functionally disrupt this circuitry over time. This thesis investigates how repeated cocaine intake affects the basal ganglia not only functionally and behaviorally, but also structurally, with particular attention to patterns of gray matter volume (GMV) change. GMV has been studied in a wide range of mental disorders and neurological diseases, including substance use disorders, but the focus has historically not been placed on the basal ganglia, despite its implications in such diseases. Drawing from decades of foundational research and more recent volumetric studies, this work identifies significant yet inconsistent GMV alterations in the basal ganglia during cocaine use disorder (CUD), including both hypertrophy and atrophy of the striatum. These divergent findings are placed within the context of key models of addiction in order to characterize the basal ganglia as a critical location of neuroadaptation in CUD. Understanding these adaptations provides a foundation for future research into biomarkers of addiction that have not been standardized before and potential therapeutic interventions.