Although several of the above studies used negatively valenced stimuli, a lingering question is whether altered sensitivity to non-drug reinforcers in addicted individuals also applies to negative reinforcers such as money loss. Studies in animals show that ‘addicted’ subjects manifest persistent drug seeking even if the drug is associated with receiving an electric shock99. In humans, hypoactivation in the right ventrolateral PFC in smokers during monetary loss, and in gamblers during monetary gain, have been reported100 (Supplementary information S5 (table)). Although more studies are clearly needed, the implication of reduced sensitivity to negative reinforcers in addiction has practical implications as, in addition to positive reinforcers (such as vouchers and privileges), negative reinforcers (such as incarceration) are increasingly being used in the management of drug abusers. Interventions could be optimized by selecting the most effective type and dose of reinforcer. Future studies could also help to ascertain whether addicted individuals may resort to taking drugs because they are easily bored, frustrated, angry or fearful, perhaps as a result of altered PFC functioning. Low threshold for experiencing any of these emotions, or
