Neurocircuitry of addiction
- PMID: 19710631
- PMCID: PMC2805560
- DOI: 10.1038/npp.2009.110
Neurocircuitry of addiction
Erratum in
- Neuropsychopharmacology. 2010 Mar;35(4):1051
Abstract
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.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3055431/bin/npp2009110f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3055431/bin/npp2009110f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3055431/bin/npp2009110f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3055431/bin/npp2009110f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3055431/bin/npp2009110f5.gif)
Similar articles
-
Neurobiology of addiction: a neurocircuitry analysis.Lancet Psychiatry. 2016 Aug;3(8):760-773. doi: 10.1016/S2215-0366(16)00104-8. Lancet Psychiatry. 2016. PMID: 27475769 Free PMC article. Review.
-
Addiction as a stress surfeit disorder.Neuropharmacology. 2014 Jan;76 Pt B(0 0):370-82. doi: 10.1016/j.neuropharm.2013.05.024. Epub 2013 Jun 6. Neuropharmacology. 2014. PMID: 23747571 Free PMC article. Review.
-
Neurocircuitry of alcohol addiction: synthesis from animal models.Handb Clin Neurol. 2014;125:33-54. doi: 10.1016/B978-0-444-62619-6.00003-3. Handb Clin Neurol. 2014. PMID: 25307567 Review.
-
Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies.Neurosci Biobehav Rev. 2014 Jan;38:1-16. doi: 10.1016/j.neubiorev.2013.10.013. Epub 2013 Nov 6. Neurosci Biobehav Rev. 2014. PMID: 24211373 Free PMC article. Review.
-
Neurobiological mechanisms and related clinical treatment of addiction: a review.Psychoradiology. 2022 Dec 16;2(4):180-189. doi: 10.1093/psyrad/kkac021. eCollection 2022 Dec. Psychoradiology. 2022. PMID: 38665277 Free PMC article. Review.
Cited by
-
Shared and unique 3D genomic features of substance use disorders across multiple cell types.medRxiv [Preprint]. 2024 Jul 19:2024.07.18.24310649. doi: 10.1101/2024.07.18.24310649. medRxiv. 2024. PMID: 39072016 Free PMC article. Preprint.
-
Deep brain stimulation for the treatment of substance use disorders: a promising approach requiring caution.Front Psychiatry. 2024 Jul 12;15:1435109. doi: 10.3389/fpsyt.2024.1435109. eCollection 2024. Front Psychiatry. 2024. PMID: 39071229 Free PMC article.
-
Voluntary Exercise Ameliorates Chronic Ethanol Withdrawal-Induced Adaptations of Opioid Receptor Expression in the Nucleus Accumbens, Dopamine Release, and Ethanol Consumption.Biomedicines. 2024 Jul 17;12(7):1593. doi: 10.3390/biomedicines12071593. Biomedicines. 2024. PMID: 39062166 Free PMC article.
-
Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry.Nat Commun. 2024 Jul 24;15(1):6264. doi: 10.1038/s41467-024-50657-7. Nat Commun. 2024. PMID: 39048565 Free PMC article.
-
Bad habits-good goals? Meta-analysis and translation of the habit construct to alcoholism.Transl Psychiatry. 2024 Jul 19;14(1):298. doi: 10.1038/s41398-024-02965-1. Transl Psychiatry. 2024. PMID: 39030169 Free PMC article. Review.
References
-
- Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV. Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend. 2006;81:313–322. - PubMed
-
- Ahmed SH, Kenny PJ, Koob GF, Markou A. Neurobiological evidence for hedonic allostasis associated with escalating cocaine use. Nat Neurosci. 2002;5:625–626. - PubMed
-
- Ahmed SH, Koob GF.1998Transition from moderate to excessive drug intake: change in hedonic set point Science 282298–300.This study showed that rats given extended access to cocaine escalate intake and show behavior consistent with an increase in hedonic set point (lower reward) for the drug. - PubMed
-
- Ahmed SH, Koob GF. Changes in response to a dopamine antagonist in rats with escalating cocaine intake. Psychopharmacology. 2004;172:450–454. - PubMed
-
- Ahmed SH, Walker JR, Koob GF. Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology. 2000;22:413–421. - PubMed
Publication types
MeSH terms
Grants and funding
- DK26741/DK/NIDDK NIH HHS/United States
- P01 DK026741-300004/DK/NIDDK NIH HHS/United States
- DA04398/DA/NIDA NIH HHS/United States
- R01 AA008459-19A1/AA/NIAAA NIH HHS/United States
- AA08459/AA/NIAAA NIH HHS/United States
- R01 DA010072-11/DA/NIDA NIH HHS/United States
- R01 AA012602/AA/NIAAA NIH HHS/United States
- R01 AA008459/AA/NIAAA NIH HHS/United States
- P60 AA006420/AA/NIAAA NIH HHS/United States
- DA04043/DA/NIDA NIH HHS/United States
- R01 DA004398/DA/NIDA NIH HHS/United States
- P50 AA006420/AA/NIAAA NIH HHS/United States
- AA06420/AA/NIAAA NIH HHS/United States
- R01 AA012602-10/AA/NIAAA NIH HHS/United States
- AA12602/AA/NIAAA NIH HHS/United States
- DA10072/DA/NIDA NIH HHS/United States
- R01 DA004398-22/DA/NIDA NIH HHS/United States
- R37 AA008459/AA/NIAAA NIH HHS/United States
- R01 DA010072/DA/NIDA NIH HHS/United States
- R01 DA004043-23/DA/NIDA NIH HHS/United States
- P01 DK026741/DK/NIDDK NIH HHS/United States
- P60 AA006420-26/AA/NIAAA NIH HHS/United States
- R01 DA004043/DA/NIDA NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical