ABSTRACT
Humans take psychoactive drugs for many reasons, including relief from withdrawal, direct hedonic effects, performance enhancement, and mood alteration.1 Although abused drugs come from different pharmacological classes (e.g. opiates, psychostimulants, alcohol, and barbiturates) and produce physiological and behavioral effects that are unique to their class (e.g. analgesia, constipation, paranoia, and sedation), research over the past quarter-century suggests that their reinforcing properties are linked to common neuroanatomical and neurochemical systems.2,3 In addition to a putative common neurobiological linkage, another hallmark of human drug abuse is the high recidivism rate when abstinence is attempted. For example, within 6 months of attempting to quit cigarette smoking, more than 95% of individuals return to regular smoking.4 In spite of extensive fundamental insight into the cellular and molecular mechanisms of action of drugs of abuse from preclinical animal and in vitro models,5,6 such knowledge has been difficult to translate into more successful behavioral and/or pharmacotherapeutic treatments. In part, this may reflect the fact that human drug abuse, although based on the interaction of drugs acting at specific molecular binding sites, is more than a simple pharmacological disease. Rather, these drugs, both acutely and in the long term, ultimately interact in complex and still poorly understood ways with specific cognitive subsystems.
