Anti-reward circuits are engaged as neuroadaptations during the development of addiction, producing aversive or stress-like states. These aversive states are manifest when the drug is removed during acute withdrawal but also during protracted abstinence.2 Thus, the within-system and between-system construct could be equally valid for the preoccupation/anticipation stage. The combination of decreases in reward function and increases in stress function in the motivational circuits of the ventral striatum, extended amygdala, and habenula is a powerful trigger of negative reinforcement that contributes to compulsive drug-seeking behaviour and addiction. Decreases in reward can be driven by overactivation of the habenula or overactivation of the dynorphin system in the ventral striatum, both of which can decrease dopamine neuron firing. Increases in stress-like states and increased responsivity to stressors could be driven by the recruitment of CRF in the amygdala and other extrahypothalamic stress systems.
