Disruption of Dopamine Homeostasis by Psychostimulants

Dopamine is a catecholamine that acts as a modulatory neurotransmitter in the central nervous system. Although dopamine levels are kept within appropriate ranges through various mechanisms, they can be disrupted by multiple factors, including external psychostimulants such as cocaine and methamphetamine. Disruption contributes to cognitive deficits and emotional dysregulation that is associated with psychostimulant-use disorders (PSUD). These stimulants interfere with the dopamine system through various mechanisms that affect its synthesis, storage, release, reuptake, and degradation. Such changes have neurobiological effects, including receptor desensitization, oxidative stress, and neuronal damage, highlighting the importance of maintaining a balanced dopamine system. This review offers a comprehensive overview of how psychostimulants like cocaine and methamphetamine disrupt dopamine synthesis, storage, release, and reuptake, examines the neurobiological consequences of these disruptions, and proposes directions for future research on mechanisms and the development of novel neuroprotective therapies.