Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

___________________________________________

Wednesday, August 26, 2009

Neurocircuitry of Addiction
Neuropsychopharmacology advance online publication 26 August 2009;

Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving).

Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex–dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control.

The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala.

The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.


Request Reprint E-Mail: gkoob@scripps.edu

_______________________________________________________________________
at