Neurocircuitry of Addiction
Open accessAbstract
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.
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Imaging studies show that cocaine craving cues increase dopamine release in the striatum, amygdala, and prefrontal cortex and opioid peptides in the anterior cingulate and frontal cortex.
“Imaging studies have also revealed that cues associated with cocaine craving increase dopamine release in the striatum, amygdala, and prefrontal cortex (anterior cingulate and medial orbitofrontal cortex) and opioid peptides in the anterior cingulate and frontal cortex.9,31,106,107”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [9]
The Ventral Striatum/Dorsal Striatum/Thalamus section (page not provided) reports that drug-associated cues increase dopamine in the dorsal striatum and that the increase correlates with craving. It also links the amygdala and prefrontal cortex to cue-induced craving, but does not report cue-induced dopamine release in those regions. The cited passages do not support increased opioid peptides in the anterior cingulate or frontal cortex. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe amygdala mediates the shift to both negative reinforcement and negative emotional states during withdrawal, which play a key role in addiction.
“The amygdala also mediates the shift to both negative rein forcement and negative emotional states during withdrawal, which play a key role in addiction (Koob and Volkow, 2010).”
From Age-dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults. (2023) · cites this paper as Koob and Volkow, 2010
In “Withdrawal/Negative Affect Stage” (page unavailable), the paper says the extended amygdala may help produce negative emotional states that promote negative reinforcement in addiction. The claim makes this proposed role definite and calls the structure simply the amygdala, whereas the paper specifies the extended amygdala, which includes other regions. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe mesolimbic dopamine system becomes compromised after chronic administration of virtually all drugs of abuse, including opioids and alcohol.
“Nevertheless, what is also evident is that the mesolimbic dopamine system becomes compromised after the chronic administration of virtually all drugs of abuse, including opioids and alcohol (Koob and Volkow, 2010;Diana, 2011).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Koob and Volkow, 2010
The Withdrawal/Negative Affect Stage section reports reduced mesolimbic dopamine activity during acute withdrawal from all major drugs of abuse in animal studies. It also describes compromised dopamine function as a hypothesis concerning particular phases of addiction. The claim omits the withdrawal and animal-study qualifiers, presenting the effect as a general consequence of chronic administration. (LLM, conf=0.86)
Experimental — accuracy not yet measuredNeuroinflammatory signaling pathways in the central nervous system contribute to neuroadaptive processes that mediate dysregulation of hyperkatifeia associated with the withdrawal/negative affect stage of the addiction cycle.
“Neuroinflammatory signaling pathways in the central nervous system are also hypothesized to contribute to neuroadaptive processes that mediate the dysregulation of hyperkatifeia that is associated with the withdrawal/negative affect stage of the addiction cycle (Koob and Volkow, 2010;Crews and Vetreno, 2016).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Koob and Volkow, 2010
The Withdrawal/Negative Affect Stage section describes neuroadaptations involving brain stress systems and negative emotional states during withdrawal. It does not identify neuroinflammatory signaling pathways as contributors to those processes or use the term “hyperkatifeia”; the molecular-plasticity passages discuss other signaling mechanisms instead. Pages are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredImpulsivity is a core predictor of addictive behaviors and of negative outcomes associated with addiction.
“Extant literature has highlighted impulsivity as a core predictor of addictive behaviors and negative outcomes associated with addiction (DeVito et al., 2020; Koob & Volkow, 2010).”
From Problematic social media use and inhibitory control among post-secondary students (2025) · cites this paper as Koob & Volkow, 2010
The Cognitive Control section calls impulse control one of the most robust cognitive risk factors for substance use disorders, supporting the addiction-risk part of the claim. The Withdrawal/Negative Affect section hypothesizes that impaired inhibitory control and impulsivity contribute to relapse, but does not establish impulsivity as a core predictor of negative outcomes generally. Page numbers were not available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
The neural correlates of Internet-gaming disorder and other Internet-use disorders may reflect a maladaptive interaction of cue-reactivity/craving and reduced prefrontal/executive functioning, as suggested for substance addictions.
“The neural correlates of Internet-gaming disorder and other Internet-use disorders (e.g., Brand et al., 2016) may reflect a maladaptive interaction of cue-reactivity/craving and reduced prefrontal/executive functioning, as suggested for substance addictions (Goldstein and Volkow, 2011;Koob and Volkow, 2010;Volkow and Fowler, 2000;Volkow et al., 2002).”
From Integrating psychological and neurobiological considerations regarding the development and maintenance of specific Internet-use disorders: An Interaction of Person-Affect-Cognition-Execution (I-PACE) model (2016) · cites this paper as Koob and Volkow, 2010
Negative reinforcement processes are associated with severe drug dependence.
“Such negative reinforcement processes are asso-ciated with severe drug dependence”
From Addiction, adolescence, and the integration of control and motivation (2011) · cites this paper as Koob and Volkow, 2010
Dopamine projections throughout the SN play important roles in reward-oriented learning, goal-directed behavior, and processing motivational stimuli by directing attention to positive, adaptive or rewarding environmental stimuli.
“Dopamine projections throughout the SN have been noted to play important roles not only in reward-oriented learning and goal-directed behavior, but also in processing motivational stimuli by directing attention to positive, adaptive or rewarding environmental stimuli (i.e., mediating the salience of environmental stimuli; Berridge, 1996; Koob and Volkow, 2010; Kroemer et al., 2014).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Koob and Volkow, 2010
Addictive substances activate dopamine-dependent saliency systems in the brain, resulting in the replacement of adaptive stimuli by more salient drug-related cues.
“Additionally, it appears that addictive substances activate dopamine-dependent saliency systems in the brain, resulting in the replacement of adaptive stimuli by more salient drug-related cues (Koob and Volkow, 2010).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Koob and Volkow, 2010
Drug addiction has been described as a process of maladaptive neuroplasticity that begins in mesolimbic reward circuits and emanates through interconnected loops in the dorsal striatum, eventually cascading to the cortex where dysregulation results in permanent changes to habitual behavior and impulsivity.
“In summary, drug addiction has been described as a process of maladaptive neuroplasticity that begins in mesolimbic reward circuits and emanates through interconnected loops in the dorsal striatum, eventually cascading to the cortex where dysregulation results in permanent changes to habitual behavior and impulsivity (Koob and Volkow, 2010).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Koob and Volkow, 2010
Chronic drug use is characterized by compulsive drug-taking behavior despite negative consequences.
“Although initial drug intake is associated with positive reinforcement and impulsive actions, chronic drug use is characterized by compulsive drug-taking behavior despite negative consequences.4, 5, 6”
From Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependent patients (2013) · cites this paper as [6]
Preference for substance-related cues to the exclusion of natural rewards may be one of the most defining features of addiction specifically relevant to other psychiatric diseases.
“For example, preference for substance-related cues to the exclusion of natural rewards may be one of the most defining features of addiction specifically relevant to other psychiatric diseases [18].”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [18]
Dominance of the anti-reward pathway may explain the negative emotions, such as malaise and dysphoria, experienced during withdrawal.
“Ultimately, this dominance of the anti-reward pathway may explain the negative emotions, such as malaise and dysphoria, experienced during withdrawal [reviewed in (14, 24)].”
From Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice (2019) · cites this paper as [24]
Similar functional imaging studies demonstrate involvement of the hippocampus and amygdala in cue-elicited craving.
“Furthermore, similar functional imaging studies demonstrate involvement of the hippocampus and amygdala in cue-elicited craving (24), suggesting the importance of memories and emotion as substrates in craving.”
From Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice (2019) · cites this paper as [24]
Frontal cortex function is relatively preserved in the early stages of addiction and is important in the subjective effects of craving, attribution of salience, and inhibitory behavioral control.
“The frontal cortex function is relatively preserved in the early stages of addiction and is important in the subjective effects of craving, attribution of salience (assignment of relative value), and inhibitory behavioral control (24).”
From Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice (2019) · cites this paper as [24]
During acute intoxication, the mesolimbic pathway becomes active and dopamine is upregulated, especially in the nucleus accumbens, giving rise to positive reinforcing symptoms such as euphoria.
“During acute intoxication, the mesolimbic pathway, comprising dopaminergic projections from the ventral tegmental area to the nucleus accumbens (NAc) and frontal cortex, becomes active and dopamine is upregulated, especially in the NAc. This gives rise to positive reinforcing symptoms, such as euphoria (hence the term reward pathway) (14, 24, 26).”
From Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice (2019) · cites this paper as [24]
The Koob and Volkow model proposes distinct neural circuits for three stages of addiction: binge/intoxication, withdrawal/negative affect, and preoccupation/craving.
“Koob and Volkow (2010) provide a comprehensive model of addiction neurobiology that proposes distinct neural circuits for three stages of addiction: binge/intoxication; withdrawal/negative affect; and preoccupation/craving addiction (also see Koob and Moal, 1997).”
From The human BNST: functional role in anxiety and addiction (2016) · cites this paper as Koob and Volkow (2010)
In the Koob and Volkow model, the BNST has a prominent role in the withdrawal/negative affect stage of addiction.
“In the Koob and Volkow model, the BNST has a prominent role in the withdrawal/negative affect stage of addiction, consistent with evidence that highlights the role of BNST in withdrawal across drugs of abuse, including alcohol (Silberman et al, 2013;Wills et al, 2012) and opiates (Wang et al, 2006;Delfs et al, 2000).”
From The human BNST: functional role in anxiety and addiction (2016) · cites this paper as Koob and Volkow (2010)
This BNST-paracingulate finding is notable because prefrontal cortex deficits are implicated in stress-related disorders such as anxiety and addiction.
“This finding is especially interesting given the role of prefrontal cortex deficits in stress-related disorders such as anxiety and addiction (Koob and Volkow, 2010;Shin and Liberzon, 2010).”
From The human BNST: functional role in anxiety and addiction (2016) · cites this paper as Koob and Volkow, 2010
Chronic nicotine exposure causes neuroadaptations that produce widespread changes in brain neurotransmission, promoting and sustaining tobacco use.
“The neuroadaptations arising from chronic nicotine exposure cause widespread alterations in brain neurotransmission that promote and sustain the use of tobacco [21–24].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [23]
Negative affective symptoms of withdrawal act as negative reinforcers that sustain addiction.
“The emergence of negative affective symptoms, such as dysphoria, anxiety and irritability and, to a lesser extent, the somatic manifestations of withdrawal, serve as negative reinforcers that sustain the vicious cycle of addiction [23, 121, 132–134].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [23]
All drugs of abuse activate the mesolimbic dopamine system reward pathway.
“All drugs of abuse activate the mesolimbic dopamine system reward pathway27, and dopamine-related genes have long been popular candidate genes.”
From Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use (2019) · cites this paper as [27]
Dopamine modulates activity within the IM circuitry to promote IM.
“Numerous animal, human pharmacological, and molecular genetic studies indicate that dopamine (DA) modulates activity within this circuitry to promote IM (Depue & Collins, 1999; Koob & Volkow, 2010).”
From Incentive Motivation, Cognitive Control, and the Adolescent Brain: Is It Time for a Paradigm Shift? (2012) · cites this paper as Koob & Volkow, 2010
Substance use affects the dopamine system's neuroplasticity in ways that can alter subsequent development.
“Substance use, for instance, affects the dopamine system’s neuroplasticity in ways that can alter subsequent development (Koob & Volkow, 2010).”
From Incentive Motivation, Cognitive Control, and the Adolescent Brain: Is It Time for a Paradigm Shift? (2012) · cites this paper as Koob & Volkow, 2010
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Kitamura, O., Wee, S., Specio, S. E., Koob, G. F., & Pulvirenti, L. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0353-z · Cited by 218 · see citing works
Self-citationThe ventral pallidum plays a role in mediating cocaine and heroin self-administration in the rat
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Self-citationVolkow, N. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)00104-9 · Cited by 217 · see citing works
Self-citationAcute Effect of Methadone Maintenance Dose on Brain fMRI Response to Heroin-Related Cues
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McGregor, A., & Roberts, D. C. S. (1993) · Brain Research · doi:10.1016/0006-8993(93)90084-z · Cited by 215 · see citing works
Watkins, S. S., Stinus, L., Koob, G. F., & Markou, A. (2000) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35389-3 · Cited by 214 · see citing works
Self-citationIs Cocaine Desire Reduced by N -Acetylcysteine?
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Neuroprotective and Abstinence-Promoting Effects of Acamprosate: Elucidating the Mechanism of Action
De Witte, P., Littleton, J., Parot, P., & Koob, G. (2005) · CNS Drugs · doi:10.2165/00023210-200519060-00004 · Cited by 201 · cited 1× · see citing works
“Protracted abstinence, largely described in alcohol dependence models, appears to involve overactive glutamatergic and CRF systems, presumably in the extended amygdala, although to a large extent this remains to be explored (de Witte et al, 2005; Valdez et al, 2002).”
BackgroundSelf-citationSleep Deprivation Decreases Binding of [11C]Raclopride to Dopamine D2/D3Receptors in the Human Brain
Volkow, N. D., Wang, G., Telang, F., Fowler, J. S., Logan, J., Wong, C., Ma, J., Pradhan, K., Tomasi, D. G., Thanos, P. K., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1443-08.2008 · Cited by 196 · see citing works
Self-citationCocaine : pharmacology, physiology, and clinical strategies
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Self-citationWolf, M. E. (2002) · Molecular Interventions · doi:10.1124/mi.2.3.146 · Cited by 185 · see citing works
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Lack of Self-Administration of Cocaine in Dopamine D <sub>1</sub> Receptor Knock-Out Mice
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Self-citationThe basal forebrain : anatomy to function
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Pattern of use and subjective effects of Salvia divinorum among recreational users
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The dopamine-containing neuron: maestro or simple musician in the orchestra of addiction?
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George, O., Mandyam, C. D., Wee, S., & Koob, G. F. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301626 · Cited by 160 · see citing works
Self-citationA psychodynamic study of a patient during experimental self-regulated re-addiction to morphine
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Development of pharmacotherapies for drug addiction: a Rosetta stone approach
Koob, G. F., Kenneth Lloyd, G., & Mason, B. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2828 · Cited by 154 · see citing works
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Relationship between psychostimulant-induced "high" and dopamine transporter occupancy.
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Acute effects of cocaine on the neurobiology of cognitive control
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Central Administration of an Opiate Antagonist Decreases Oral Ethanol Self-Administration in Rats
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Delay Discounting Correlates with Proportional Lateral Frontal Cortex Volumes
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Self-citationD1 dopamine receptor stimulation increases GluR1 surface expression in nucleus accumbens neurons
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- American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 1994 American Psychiatric Press Washington, DC 4th edn
- Hebb DO Textbook of Psychology 1972 WB Saunders Philadelphia 3rd edn
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Neurobiology of addiction: a neurocircuitry analysis
Koob, G. F., & Volkow, N. D. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)00104-8 · Cited by 3,698 · see citing works
“Modified from Koob and Volkow (2010)9 with permission from Nature Publishing Group.”
MethodSelf-citationThe physiology, signaling, and pharmacology of dopamine receptors
Beaulieu, J.-M., & Gainetdinov, R. R. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002642 · Cited by 2,763 · see citing works
Brand, M., Young, K. S., Laier, C., Wölfling, K., & Potenza, M. N. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.08.033 · Cited by 2,153 · see citing works
“…ther Internet-use disorders (e.g., Brand et al., 2016) may reflect maladaptive interaction of cue-reactivity/craving and reduced refrontal/executive functioning, as suggested for substance addicions (Goldstein and Volkow, 2011; Koob and Volkow, 2010; olkow and Fowler, 2000; Volkow et al., 2002).”
Brand, M., Wegmann, E., Stark, R., Müller, A., Wölfling, K., Robbins, T. W., & Potenza, M. N. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.06.032 · Cited by 2,126 · see citing works
Neurobiologic advances from the brain disease model of addiction
Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1511480 · Cited by 2,008 · see citing works
Self-citationInhibition and impulsivity: behavioral and neural basis of response control
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Annual research review: enduring neurobiological effects of childhood abuse and neglect
Teicher, M. H., & Samson, J. A. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12507 · Cited by 1,473 · see citing works
Drug addiction: updating actions to habits to compulsions ten years on
Everitt, B. J., & Robbins, T. W. (2016) · Annual Review of Psychology · doi:10.1146/annurev-psych-122414-033457 · Cited by 1,225 · see citing works
Harnessing neuroplasticity for clinical applications
Cramer, S. C., Sur, M., Dobkin, B. H., O'Brien, C., Sanger, T. D., Trojanowski, J. Q., Rumsey, J. M., Hicks, R., Cameron, J., Chen, D., et al. (2011) · Brain · doi:10.1093/brain/awr039 · Cited by 1,259 · see citing works
Tyrosine hydroxylase and regulation of dopamine synthesis
Daubner, S. C., Le, T., & Wang, S. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.12.017 · Cited by 1,092 · see citing works
Distinct roles for direct and indirect pathway striatal neurons in reinforcement
Kravitz, A. V., Tye, L. D., & Kreitzer, A. C. (2012) · Nature Neuroscience · doi:10.1038/nn.3100 · Cited by 972 · see citing works
Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889 · see citing works
The Vertebrate mesolimbic reward system and social behavior network: A comparative synthesis
O'Connell, L. A., & Hofmann, H. A. (2011) · Journal of Comparative Neurology · doi:10.1002/cne.22735 · Cited by 986 · see citing works
Haber, S. N. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.1/shaber · Cited by 922 · see citing works
The Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863 · see citing works
Self-citationCerebellar networks with the cerebral cortex and basal ganglia
Bostan, A. C., Dum, R. P., & Strick, P. L. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.03.003 · Cited by 759 · see citing works
Reward mechanisms in obesity: new insights and future directions
Kenny, P. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.016 · Cited by 748 · see citing works
Sex Differences in Animal Models: Focus on Addiction
Becker, J. B., & Koob, G. F. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011163 · Cited by 725 · see citing works
Self-citationStreeter, C. C., Gerbarg, P. L., Saper, R. B., Ciraulo, D. A., & Brown, R. P. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.01.021 · Cited by 694 · see citing works
From prediction error to incentive salience: mesolimbic computation of reward motivation.
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From the ventral to the dorsal striatum: devolving views of their roles in drug addiction
Everitt, B. J., & Robbins, T. W. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.02.010 · Cited by 675 · see citing works
Peters, S. K., Dunlop, K., & Downar, J. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00104 · Cited by 611 · see citing works
“Impulsivity and compulsivity are well-characterized traits of SUD, and both traits play important roles in the addiction cycle (Koob and Volkow, 2010).”
BackgroundInfluentialStrang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639 · see citing works
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Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance
Stamatakis, A. M., & Stuber, G. D. (2012) · Nature Neuroscience · doi:10.1038/nn.3145 · Cited by 564 · see citing works
Prevention and Treatment of Opioid Misuse and Addiction: A Review
Volkow, N. D., Jones, E. B., Einstein, E. B., & Wargo, E. M. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2018.3126 · Cited by 596 · see citing works
Self-citationSchacht, J. P., Anton, R. F., & Myrick, H. (2013) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00464.x · Cited by 583 · see citing works
Cannabis use and cannabis use disorder
Connor, J. P., Stjepanović, D., Le Foll, B., Hoch, E., Budney, A. J., & Hall, W. D. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00247-4 · Cited by 552 · see citing works
Wiers, R. W., Gladwin, T. E., Hofmann, W., Salemink, E., & Ridderinkhof, K. R. (2013) · Clinical Psychological Science · doi:10.1177/2167702612466547 · Cited by 486 · see citing works
Dean, O., Giorlando, F., & Berk, M. (2011) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100057 · Cited by 494 · see citing works
Volkow, N. D., & Blanco, C. (2023) · World psychiatry · doi:10.1002/wps.21073 · Cited by 503 · see citing works
Self-citationNeurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477 · see citing works
Self-citationMaintenance Medication for Opiate Addiction: The Foundation of Recovery
Bart, G. (2012) · Journal of Addictive Diseases · doi:10.1080/10550887.2012.694598 · Cited by 461 · see citing works
Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings
Panenka, W. J., Procyshyn, R. M., Lecomte, T., MacEwan, G. W., Flynn, S. W., Honer, W. G., & Barr, A. M. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2012.11.016 · Cited by 432 · see citing works
The promise of N-acetylcysteine in neuropsychiatry
Berk, M., Malhi, G. S., Gray, L. J., & Dean, O. M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.01.001 · Cited by 434 · see citing works
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Addictions neuroclinical assessment: a neuroscience-based framework for addictive disorders
Kwako, L. E., Momenan, R., Litten, R. Z., Koob, G. F., & Goldman, D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.024 · Cited by 395 · see citing works
Self-citationAdamantidis, A. R., Tsai, H.-C., Boutrel, B., Zhang, F., Stuber, G. D., Budygin, E. A., Tourino, C., Bonci, A., Deisseroth, K., & de Lecea, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2246-11.2011 · Cited by 357 · see citing works
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
“When access to nicotine is not available, these homeostatic neuroadaptations are no longer appropriate, which contributes to the withdrawal syndrome (Koob & Volkow 2009).”
BackgroundModel-based and model-free Pavlovian reward learning: Revaluation, revision, and revelation
Dayan, P., & Berridge, K. C. (2014) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-014-0277-8 · Cited by 357 · see citing works
The human BNST: functional role in anxiety and addiction
Avery, S. N., Clauss, J. A., & Blackford, J. U. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.185 · Cited by 331 · see citing works
One Is Not Enough: Understanding and Modeling Polysubstance Use
Crummy, E. A., O’Neal, T. J., Baskin, B. M., & Ferguson, S. M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00569 · Cited by 351 · see citing works
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337 · see citing works
Self-citationNatural rewards, neuroplasticity, and non-drug addictions
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Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats
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The role of neuroimmune signaling in alcoholism
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Everitt, B. J. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12644 · Cited by 318 · see citing works
Addiction and Stress: An Allostatic View
Koob, G. F., & Schulkin, J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.008 · Cited by 315 · see citing works
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Common brain mechanisms of chronic pain and addiction
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Induction of innate immune genes in brain create the neurobiology of addiction
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Addiction, adolescence, and the integration of control and motivation
Gladwin, T. E., Figner, B., Crone, E. A., & Wiers, R. W. (2011) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2011.06.008 · Cited by 296 · see citing works
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Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology
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Neural mechanisms of social homeostasis
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Terraneo, A., Leggio, L., Saladini, M., Ermani, M., Bonci, A., & Gallimberti, L. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.011 · Cited by 281 · see citing works
Epigenetic Regulation of the BDNF Gene: Implications for Psychiatric Disorders
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Gambling Disorder and Other Behavioral Addictions: Recognition and Treatment
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“Though not an exhaustive model of the time-course of addiction, we focus here on three primary systems where neuroscience models of addiction from the extant literature converge to shed light on dysregulated behavioral control: (1) habit responding-automaticity (Figure 1A), (2) unregulated craving (Figure 1B), and (3)…”
BackgroundInfluentialAnticipatory reward processing in addicted populations: a focus on the monetary incentive delay task
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Neuroscience of Internet Pornography Addiction: A Review and Update
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- Authors
- Koob, G. F., & Volkow, N. D.
- Affiliations
- Scripps Research Institute (US)
- National Institute on Drug Abuse (US)
- Corresponding author
- Koob, George F
- Venue
- Neuropsychopharmacology
- Published
- 2009-08-26
- Volume
- 35
- Issue
- 1
- Pages
- 217-238
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2805560
- OpenAlex
- W2066848874
- Cited by
- 5,340
- References
- 252
- Citations by year
- 2026: 257 · 2025: 333 · 2024: 319 · 2023: 357 · 2022: 307 · 2021: 352 · 2020: 365 · 2019: 313 · 2018: 340 · 2017: 354 · 2016: 399 · 2015: 374 · 2014: 353 · 2013: 345 · 2012: 267
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-01-13)
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tobacco-Related Disease Research Program
- National Institutes of Health (AA06420, AA08459, DK-26741)
- National Institute on Alcohol Abuse and Alcoholism (R01AA008459, AA12602, AA-06420, AA-08459, P50AA006420, R37AA008459, R01AA012602, P60AA006420)
- National Institute on Drug Abuse (R01DA010072, DA04043, DA04398, DA-10072, AA06420, R01DA004398, R01DA004043)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- drug addiction, neurocircuitry, addiction cycle, withdrawal, craving, ventral tegmental area, ventral striatum, extended amygdala, orbitofrontal cortex, prefrontal cortex, mesolimbic dopamine system, neuroplasticity, impulsivity, compulsivity, inhibitory control, addiction vulnerability
- MeSH terms
- Animals, Brain, Humans, Models, Neurological, Neural Pathways, Substance-Related Disorders
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