Brain Disorders Due to Addictive Substance Use and Their Association with Excitotoxicity
Brain Disorders Due to Addictive Substance Use and Their Association with Excitotoxicity
Keywords:
Mesolimbic pathway, glutamate, dopamine, drugs of abuse, neuronal damageAbstract
Drug use disorders involve multiple brain regions linked to reward, emotion, memory, impulse control, and motor function. Among the most affected areas are the mesolimbic dopaminergic system, the prefrontal cortex, the hippocampus, the amygdala, the cerebellum, and the basal ganglia; these structures show changes that vary with the stage and severity of addiction. Addiction is described as a chronic brain disease characterized by compulsive use, loss of control, and negative emotional states during withdrawal.
A key cellular basis of damage is excitotoxicity, mainly driven by dysregulation of the glutamatergic system. Excess glutamate triggers neurotoxic processes that impair neuronal communication and synaptic plasticity, contributing to cognitive decline, compulsive habits, and reduced executive control. In this framework, interactions between glutamate and dopamine become particularly relevant in regions such as the ventral tegmental area, nucleus accumbens, and prefrontal cortex, where they influence the development and maintenance of addictive disorders. Together, these mechanisms point to an integrated brain network that becomes imbalanced with continued exposure to substances or addictive behaviors, perpetuating vulnerability and hindering recovery.
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Copyright (c) 2025 Rafael de Jesús Macias Vélez, Andrea Reyes Rivera, Martha Catalina Rivera Cervantes, Jorge Peregrina Sandoval
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