Which substance, when used chronically, can lead to a hypodopaminergic state?

The substance that, when used chronically, can lead to a hypodopaminergic state is cocaine. Chronic cocaine use is associated with significant neuroadaptations in the brain's reward circuitry. Initially, cocaine increases dopamine levels by blocking the reuptake of dopamine in the synaptic cleft, leading to heightened feelings of euphoria and increased motivation. However, over time, the persistent stimulation of dopamine receptors causes the brain to adjust by downregulating these receptors and reducing overall dopamine neurotransmission.

As a result, when an individual stops using cocaine, they may experience a marked decrease in dopamine activity, leading to symptoms associated with a hypodopaminergic state, such as anhedonia, lack of motivation, and depression. This dysregulation of dopamine is a critical factor in cocaine addiction and withdrawal, reflecting how chronic use can ultimately impair the brain’s natural reward system.