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Addiction. 2006 Sep;101 Suppl 1:23-30.

The neurobiology of addiction: a neuroadaptational view relevant for diagnosis.

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Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA.



The purpose of this review is to provide a synthesis of our knowledge of the neurobiological bases of addiction relevant for the diagnosis of addiction.


A heuristic framework of neuroadaptive changes within key brain neurocircuitry responsible for different stages of the addiction cycle is outlined and linked to human studies to provide important future translational links for diagnosis.


Animal studies have revealed dysregulation of specific neurochemical mechanisms (dopamine, opioid peptides) in the brain reward systems and recruitment of brain stress systems (corticotropin-releasing factor) during the development of dependence that convey vulnerability to relapse. Animal studies have implicated the prefrontal cortex and basolateral amygdala in drug- and cue-induced relapse, respectively, and the brain stress systems in stress-induced relapse. Genetic studies suggest roles for the genes encoding the neurochemical elements involved in both the brain reward and stress systems in the vulnerability to addiction, and molecular studies have identified transduction and transcription factors that may mediate dependence-induced reward dysregulation. Human imaging studies reveal similar neurocircuits involved in acute intoxication, chronic drug dependence and vulnerability to relapse.


Major neurobiological changes in substance abuse disorders common to human and animal studies relevant for diagnosis include a compromised reward system, overactivated brain stress systems and compromised orbitofrontal/prefrontal cortex function. No biological markers of substance abuse disorders currently exist, but there are many promising neurobiological features of substance abuse disorders that will eventually aid in the specific diagnoses of substance use, misuse and dependence.

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