Neurobiological mechanisms underlying psychostimulant use

Rates of individuals struggling with psychostimulant use disorder (PSUD), defined as chronic use of psychostimulants despite negative consequences, are growing rapidly over the last few decades. However, there are no current pharmacotherapeutics to aid individuals in maintaining drug abstinence. Identifying the underlying neurobiological mechanisms that promote persistent craving and taking of psychostimulants is critical to creating novel pharmacological treatments for PSUD. Psychostimulant use dysregulates processes within the brain that are responsible for decision-making, reward, and memory formation to drive future drug-seeking. Here, we describe novel findings and theories on how psychostimulants impact mechanisms related to transcription, mitochondrial function, and synaptic plasticity within the reward system to drive drug-seeking. We also highlight work examining how psychostimulants impact neural networks through rewiring circuitry to drive addiction-related behaviors. Overall, this review aims to feature the latest progress in understanding the biological basis of PSUD and promising mechanisms for PSUD pharmacotherapeutics.