Experimental medicine in drug addiction: towards behavioral, cognitive and neurobiological biomarkers

Several theoretical frameworks have been developed to understand putative processes and mechanisms involved in addiction. Whilst these 'theories of addiction' disagree about importance and/or nature of a number of key psychological processes (e.g. the necessity of craving and/or the involvement of drug-value representations), a number of commonalities exist. For instance, it is widely accepted that Pavlovian associations between cues and environmental contexts and the drug effects acquired over the course of addiction play a critical role, especially in relapse vulnerability in detoxified addicts. Additionally, all theories of addiction (explicitly or implicitly) propose that chronic drug exposure produces persistent neuroplastic changes in neurobiological circuitries underlying critical emotional, cognitive and motivational processes, although disagreement exists as to the precise nature of these neurobiological changes and/or their psychological consequences. The present review, rather than limiting itself to any particular theoretical stance, considers various candidate psychological, neurobiological and/or behavioral processes in addiction and outlines conceptual and procedural approaches for the experimental medicine laboratory. The review discusses (1) extinction, renewal and (re)consolidation of learned associations between cues and drugs, (2) the drug reward value, (3) motivational states contributing to drug seeking and (4) reflective (top-down) and sensory (bottom-up) driven decision-making. In evaluating these psychological and/or behavioral processes and their relationship to addiction we make reference to putative underlying brain structures identified by basic animal studies and/or imaging studies with humans.