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This unified model has undergone a dramatic revision, and reward and addiction are now conceptualized as distinct neurochemical processes involving different, albeit overlapping, neuroanatomical circuits. Especially puzzling was a preclinical study exploring ventral striatal DA release and cocaine self-administration in DAT-deficient mice. The attenuated D2 striatal concentrations were hypothesized to lessen the reinforcing salience of natural rewards and to heighten the need for substance-induced elevations in dopaminergic efflux.

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