Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli

Drug abuse and dependence define behavioral states involving increased allo cation of behavior towards drug seeking and taking at the expense of more a ppropriate behavioral patterns. As such. addiction can be viewed as increas ed control of behavior by the desired drug (due to its unconditioned, rewar ding properties). It is also clear that drug-associated (conditioned) stimu li acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentiv e learning processes. New data are emerging that suggest that regions of th e frontal cortex involved in inhibitory response control are directly affec ted by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability t o inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavio r may thus be due to two related phenomena: (1) augmented incentive motivat ional qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neuroche mical substrates subserving inhibitory control and motivational processes i n the rodent and primate brain and their putative impact on drug seeking. T he evidence for cognitive impulsivity in drug abuse associated with dysfunc tion of the frontostriatal system will be discussed, and an integrative hyp othesis for compulsive reward-seeking in drug abuse will be presented.