Individual differences in prefrontal cortex function and the transition from drug use to drug dependence

Neurosci Biobehav Rev. 2010 Nov;35(2):232-47. doi: 10.1016/j.neubiorev.2010.05.002. Epub 2010 May 20.


Several neuropsychological hypotheses have been formulated to explain the transition to addiction, including hedonic allostasis, incentive salience, and the development of habits. A key feature of addiction that remains to be explored is the important individual variability observed in the propensity to self-administer drugs, the sensitivity to drug-associated cues, the severity of the withdrawal state, and the ability to quit. In this review, we suggest that the concept of self-regulation, combined with the concept of modularity of cognitive function, may aid in the understanding of the neural basis of individual differences in the vulnerability to drugs and the transition to addiction. The thesis of this review is that drug addiction involves a failure of the different subcomponents of the executive systems controlling key cognitive modules that process reward, pain, stress, emotion, habits, and decision-making. A subhypothesis is that the different patterns of drug addiction and individual differences in the transition to addiction may emerge from differential vulnerability in one or more of the subcomponents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amygdala / physiopathology
  • Animals
  • Behavior, Addictive / physiopathology
  • Behavior, Addictive / psychology
  • Cognition / physiology
  • Disease Progression
  • Dopamine / physiology*
  • Executive Function / physiology
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Individuality*
  • Opioid Peptides / physiology
  • Pituitary-Adrenal System / physiopathology
  • Prefrontal Cortex / physiopathology*
  • Social Control, Informal
  • Substance-Related Disorders / physiopathology*
  • Substance-Related Disorders / psychology


  • Opioid Peptides
  • Dopamine