Neurobiological mechanisms in the transition from drug use to drug dependence

George F. Koob, Serge H. Ahmed, Benjamin Boutrel, Scott A. Chen, Paul J. Kenny, Athina Markou, Laura E. O'Dell, Loren H. Parsons, Pietro Paolo Sanna

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432 Scopus citations


Drug addiction is a chronic relapsing disorder characterized by compulsive drug intake, loss of control over intake, and impairment in social and occupational function. Animal models have been developed for various stages of the addiction cycle with a focus in our work on the motivational effects of drug dependence. A conceptual framework focused on allostatic changes in reward function that lead to excessive drug intake provides a heuristic framework with which to identify the neurobiologic mechanisms involved in the development of drug addiction. Neuropharmacologic studies in animal models have provided evidence for the dysregulation of specific neurochemical mechanisms in specific brain reward and stress circuits that provide the negative motivational state that drives addiction. The allostatic model integrates molecular, cellular and circuitry neuroadaptations in brain motivational systems produced by chronic drug ingestion with genetic vulnerability, and provides a new opportunity to translate advances in animal studies to the human condition.

Original languageEnglish
Pages (from-to)739-749
Number of pages11
JournalNeuroscience and Biobehavioral Reviews
Issue number8
StatePublished - Jan 2004
Externally publishedYes


  • Drug dependence Allostasis
  • Dysregulation
  • Vulnerability


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