This review explores the neural mechanisms underlying the transition from voluntary drug use to compulsive drug-seeking and addiction. The authors propose that drug addiction represents a series of transitions from initial voluntary drug use through loss of control, leading to habitual and ultimately compulsive drug-seeking behavior. This transition involves a shift from prefrontal cortical to striatal control over drug-seeking and drug-taking behaviors, as well as a progression from ventral to more dorsal domains of the striatum, mediated by its dopaminergic circuitry. Chronic drug self-administration induces neuroplasticity in both cortical and striatal structures, including long-lasting changes due to toxic drug effects. The review also highlights evidence that impulsivity, a trait associated with low dopamine D2/3 receptors in the nucleus accumbens, predicts both the escalation of cocaine intake and the switch to compulsive drug-seeking and addiction. The transition from voluntary to habitual drug-seeking is linked to a shift from ventral to dorsal striatal control. The nucleus accumbens shell (AcbS) and ventral striatum are involved in the reinforcing effects of drugs, while the dorsal striatum is associated with habitual drug-seeking. Dopamine release in the dorsal striatum is crucial for the maintenance of drug-seeking behavior. The study also shows that the acquisition of cocaine-seeking behavior depends on the integrity of the nucleus accumbens core (AcbC) and its connections from the basolateral amygdala (BLA). Lesions in these areas impair the acquisition of cocaine-seeking behavior, while simple drug-taking is not affected. The shift from ventral to dorsal striatal control is supported by evidence that dopamine receptor antagonists in the dorsal striatum impair habitual cocaine-seeking. This suggests that the dorsal striatum mediates well-established drug-seeking habits. The study also shows that the development of S–R habits is influenced by the strength of the response-outcome contingency, with interval schedules promoting the development of S–R habits more rapidly than ratio schedules. Impulsivity, characterized by premature responses in a five-choice serial reaction-time task, is associated with low dopamine D2/3 receptor availability in the ventral striatum and predicts the escalation of cocaine intake and the switch to compulsive drug-seeking. Impulsive rats show increased cocaine intake and are more likely to relapse after abstinence. Neurobiological studies show that impulsive rats have reduced fallypride binding in the ventral striatum, correlating with impulsivity and increased cocaine intake. The review also discusses the role of dopamine D2/3 receptors in vulnerability to addiction, with low receptor availability in the ventral striatum linked to impulsivity and increased cocaine intake. The study highlights the importance of the ventral striatum in the neural mechanisms underlying the propensity to seek and work for cocaine over extended periods. The findings suggest that the shift from ventral to dorsal striatal control is a key factor in the development of compulsive drug-seeking behavior. The review concludesThis review explores the neural mechanisms underlying the transition from voluntary drug use to compulsive drug-seeking and addiction. The authors propose that drug addiction represents a series of transitions from initial voluntary drug use through loss of control, leading to habitual and ultimately compulsive drug-seeking behavior. This transition involves a shift from prefrontal cortical to striatal control over drug-seeking and drug-taking behaviors, as well as a progression from ventral to more dorsal domains of the striatum, mediated by its dopaminergic circuitry. Chronic drug self-administration induces neuroplasticity in both cortical and striatal structures, including long-lasting changes due to toxic drug effects. The review also highlights evidence that impulsivity, a trait associated with low dopamine D2/3 receptors in the nucleus accumbens, predicts both the escalation of cocaine intake and the switch to compulsive drug-seeking and addiction. The transition from voluntary to habitual drug-seeking is linked to a shift from ventral to dorsal striatal control. The nucleus accumbens shell (AcbS) and ventral striatum are involved in the reinforcing effects of drugs, while the dorsal striatum is associated with habitual drug-seeking. Dopamine release in the dorsal striatum is crucial for the maintenance of drug-seeking behavior. The study also shows that the acquisition of cocaine-seeking behavior depends on the integrity of the nucleus accumbens core (AcbC) and its connections from the basolateral amygdala (BLA). Lesions in these areas impair the acquisition of cocaine-seeking behavior, while simple drug-taking is not affected. The shift from ventral to dorsal striatal control is supported by evidence that dopamine receptor antagonists in the dorsal striatum impair habitual cocaine-seeking. This suggests that the dorsal striatum mediates well-established drug-seeking habits. The study also shows that the development of S–R habits is influenced by the strength of the response-outcome contingency, with interval schedules promoting the development of S–R habits more rapidly than ratio schedules. Impulsivity, characterized by premature responses in a five-choice serial reaction-time task, is associated with low dopamine D2/3 receptor availability in the ventral striatum and predicts the escalation of cocaine intake and the switch to compulsive drug-seeking. Impulsive rats show increased cocaine intake and are more likely to relapse after abstinence. Neurobiological studies show that impulsive rats have reduced fallypride binding in the ventral striatum, correlating with impulsivity and increased cocaine intake. The review also discusses the role of dopamine D2/3 receptors in vulnerability to addiction, with low receptor availability in the ventral striatum linked to impulsivity and increased cocaine intake. The study highlights the importance of the ventral striatum in the neural mechanisms underlying the propensity to seek and work for cocaine over extended periods. The findings suggest that the shift from ventral to dorsal striatal control is a key factor in the development of compulsive drug-seeking behavior. The review concludes