Indeed, through conditioning, a neutral stimulus that is linked with the reinforcer (in this case, the drug) acquires the ability—on its own—to increase DA in the NAc in anticipation of the reward, and preclinical studies have shown that this effect is associated with drug-seeking behaviors (27). When exposed to a conditioned stimulus, the DA neurons in animals trained to expect a natural reinforcer (e.g., food) stop responding to the primary reinforcer and instead respond to the conditioned stimulus (23). These studies have also shown that, when the reward is expected and does not occur, DA cell firing is inhibited and DA release in the NAc is decreased. Thus, at this time, we cannot rule out the possibility that the decreases in BOLD detected through fMRI studies in the NAc of cocaine abusers after intravenous cocaine administration could reflect a decreased deactivation as a response to a drug whose effects are not as intense as may have been expected.
