Which neurotransmitter system, beyond dopamine and norepinephrine, is significantly affected by cocaine, contributing to its addictive properties?

Beyond dopamine and norepinephrine, the serotonin neurotransmitter system is significantly affected by cocaine, contributing to its addictive properties. Cocaine acts as a reuptake inhibitor for serotonin by blocking the serotonin transporter (SERT). The serotonin transporter is responsible for removing serotonin from the synapse back into the presynaptic neuron. By blocking SERT, cocaine prevents serotonin reuptake, leading to an increase in serotonin levels in the synapse. This increase in serotonin contributes to various effects, including mood elevation and changes in reward processing, which can reinforce drug-seeking behavior and contribute to addiction. While the dopaminergic effects of cocaine are primarily associated with its euphoric and reinforcing properties, the serotonergic effects also play a significant role in modulating mood, impulsivity, and decision-making processes related to drug use. The combined effects of cocaine on dopamine, norepinephrine, and serotonin systems contribute to the complex neurobiological mechanisms underlying cocaine addiction. The serotonergic effects are particularly relevant in understanding the compulsive aspects of cocaine use and the difficulties individuals face in abstaining from the drug.