Sensitization processes in drug addiction

In 1993, Robinson and Berridge published their first review that laid out the incentive sensitization theory of addiction (Robinson and Berridge 1993 Brain Res Rev 18:247). Its basic point is that repeated exposure to drugs of abuse causes hypersensitivity to drugs and drug-associated stimuli of the neural circuits mediating incentive salience, an important way in which motivational stimuli influence behavior. In laymen's terms, it states that this drug-induced hypersensitivity of motivational circuitry would mediate an increase in drug "wanting," thus being responsible for the dramatically exaggerated motivation for drugs displayed by addicts. This theory has been exceptionally influential, as evidenced by the fact that the original review paper about this theory (Robinson and Berridge 1993 Brain Res Rev 18:247) has been cited 2,277 times so far, and subsequent updates of this view (Robinson and Berridge 2000 Addiction 95(Suppl 2):S91; Robinson and Berridge 2001 Addiction 96:103; Robinson and Berridge 2003 Ann Rev Psychol 54:25) have been cited 274, 297, and 365 times, respectively, adding up to more than 3,200 citations within 15 years. The present chapter aims to delineate the merits and limitations of the incentive sensitization view of addiction, and whether incentive sensitization occurs in humans. We conclude that since incentive sensitization most prominently occurs after the first few drug exposures, it may represent an important initial step in the addiction process. During the expression of full-blown addiction, characterized by loss of control over drug intake and use of large quantities of drugs, the expression of incentive sensitization may be transiently suppressed. However, detoxification and the gradual disappearance of tolerance and withdrawal symptoms may unmask sensitization, which could then play an important role in the high risk of relapse.