Figure 2

Drug-induced changes in phasic and tonic dopamine transmission in the NAcc (a) In the drug-naïve state, phasic (triangles) and tonic (solid horizontal line) dopamine signaling in the NAcc is normal. Few spontaneous phasic dopamine events (no cue) are observed. Salient stimuli (non-drug cues) can elicit phasic dopamine release and goal-directed behavior. (b) Drugs of abuse enhance tonic (dashed line) and phasic (triangles) dopamine signaling. Stimuli not associated with drug (non-drug cues) and drug-related cues both elicit phasic dopamine events, but the latter cause more robust release due to the temporal proximity to the drug administration. Furthermore, the number of spontaneous phasic dopamine events is increased. This may lead to aberrant learning of drug-cue associations and thus abnormal goal-directed behavior such as compulsive drug taking. (c) Effects of drug withdrawal on dopamine signaling are variable. For example, dampened tonic dopamine concentrations during withdrawal can be returned to and above basal concentrations by exposure to drug cues and drug context (left to right). Such drug cues may also elicit more phasic dopamine release (dashed triangle) compared to non-drug cues because 1) drugs represent a higher reward magnitude than natural reinforcers and/or 2) extended withdrawal results in incubation of drug craving. As a consequence, independent of tonic dopamine levels, seeking for drugs is more prevalent than seeking for natural reinforcers, which may promote relapse to drug taking.