to form the neurobiological basis for the b-process: loss of function in the reward systems (within-system neuroadaptation) and recruitment of the brain stress or anti-reward systems (between-system neuroadaptation) (Koob and Bloom, 1988; Koob and Le Moal, 1997). Anti-reward is a construct based on the hypothesis that brain systems are in place to limit reward (Koob and Le Moal, 2008). As dependence and withdrawal develop, brain stress systems such as CRF, norepinephrine, and dynorphin are recruited, producing aversive or stress-like states (Koob, 2003; Nestler, 2001; Aston-Jones et al., 1999). At the same time, within the motivational circuits of the ventral striatum-extended amygdala, reward function decreases. The combination of decreases in reward neurotransmitter function and recruitment of anti-reward systems provides a powerful source of negative reinforcement that contributes to compulsive drug-seeking behavior and addiction (Figure 6).
