The DOI matches its Crossref record; 183 of the 184 references it cites were found in a registry or an index.
Neurobiology of dysregulated motivational systems in drug addiction
Open accessAbstract
The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“and the upregulation of a postsynaptic Gs/cAMP/PKA signalling pathway in the nucleus accumbens might constitute a critical neuroadaptation that is central to the establishment and maintenance of the addicted state.136,137”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [137]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
The neural basis of drug craving: An incentive-sensitization theory of addiction
Robinson, T. (1993) · Brain Research Reviews · doi:10.1016/0165-0173(93)90013-p · Cited by 7,346
Di Chiara, G., & Imperato, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5274 · Cited by 4,733
Aston-Jones, G., & Cohen, J. D. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135709 · Cited by 4,472
Olds, J., & Milner, P. (1954) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058775 · Cited by 3,176
Drug Addiction, Dysregulation of Reward, and Allostasis
Koob, G. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00195-0 · Cited by 2,953
Self-citationThe Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Hyman, S. E., Malenka, R. C., & Nestler, E. J. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.113009 · Cited by 2,647
Drug abuse: hedonic homeostatic dysregulation
Koob, G. F., & Moal, M. L. (1997) · Science · doi:10.1126/science.278.5335.52 · Cited by 2,535
Self-citationCellular and molecular mechanisms of drug dependence
Koob, G. F., & Bloom, F. E. (1988) · Science · doi:10.1126/science.2903550 · Cited by 2,070
Self-citation
Flagged first, then by citations
1 of the 184 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- American Psychiatric Association: Diagnositc and Statistical Manual of Mental Disorders (4th Edition) . American Psychiatric Press Washington DC USA (2000).
- Whisler K , HallS, EdwardsS, AkkentliF, SelfDW: Tonic activation of NAc PKA signaling facilitates D2 receptor-mediated relapse to cocaine seeking and locomotor activity.Abstr. Soc. Neurosci.29, 420.417 (2003).
- Larson EB , WhislerK, SmagulaCet al.: Preferential over-expression of Gs-α in direct and indirect striatal output pathways differentially alters cocaine-taking and -seeking behaviors.Soc. Neurosci. Abstr.35 (2009) (Abstract 649.11).
- Renthal W , TerziD, OlsonEN, NestlerEJ, ZachariouV: Histone deacetylase 5 controls analgesic responsiveness to tricyclic antidepressants in a mouse model of neuropathic pain.Soc. Neurosci. Abstr.34 (2008) (Abstract 368.6).
Cited by
Sorted by citations
Items 101–157 of 157
Dennis, T. S., Beck, K. D., Bobzean, S. A. M., Dougall, A. L., & Perrotti, L. I. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.08.005 · Cited by 7
Dysregulation of c-Jun N-terminal kinase phosphorylation in alcohol dependence
Pahng, A. R., Paulsen, R. I., McGinn, M. A., Farooq, M. A., Edwards, K. N., & Edwards, S. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.04.006 · Cited by 7
Self-citationLee, S., & Edwards, S. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114867 · Cited by 6
Self-citationNeurobiology of an endophenotype: modeling the progression of alcohol addiction in rodents
Mahoney, M. K., & Olmstead, M. C. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.03.006 · Cited by 8
Song, S.-H., Jang, W., Jang, E. Y., Kim, O., Kim, H., Son, T., Choi, D., Lee, S., & Jeong, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.997701 · Cited by 6
O’Mahony, S. (2019) · Irish Journal of Sociology · doi:10.1177/0791603519835437 · Cited by 6
Kaiyala, K. J., & Ramsay, D. S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194794 · Cited by 6
Barattini, A. E., Gilpin, N. W., & Pahng, A. R. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173890 · Cited by 5
Bant, L., & Bogaerts, S. (2024) · Criminal Justice and Behavior · doi:10.1177/00938548241296491 · Cited by 5
Umpierrez, L. S., Freese, L., Almeida, F. B., Costa, P. A., Fernandes, P. R., Nin, M. S., de Souza, M. F., & Barros, H. M. T. (2021) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2021.173315 · Cited by 5
Nejad, G. G., Mottarlini, F., Tavassoli, Z., Caffino, L., Fumagalli, F., Homberg, J. R., & Fathollahi, Y. (2024) · Addiction Biology · doi:10.1111/adb.13377 · Cited by 4
Carl, E. M., Liskiewicz, A., Rivard, C., Alberico, R. A., Belal, A., Mahoney, M. C., Quisenberry, A. J., Bickel, W. K., & Sheffer, C. E. (2020) · BMC Psychology · doi:10.1186/s40359-020-00403-7 · Cited by 6
Hill-Bowen, L. D., Riedel, M. C., Poudel, R., Salo, T., Flannery, J. S., Camilleri, J. A., Eickhoff, S. B., Laird, A. R., & Sutherland, M. T. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.26.966549 · Cited by 6
Ferguson, T. F., Beauchamp, A., Rosen, E. M., Ray, A. N., Theall, K. P., Gilpin, N. W., Molina, P. E., & Edwards, S. (2020) · Frontiers in Public Health · doi:10.3389/fpubh.2020.00314 · Cited by 4
Self-citationJennings, S. D., Hagarty, D. P., Logue, J. B., Crawford, M., Saland, S. K., & Kabbaj, M. (2025) · eNeuro · doi:10.1523/eneuro.0452-24.2025 · Cited by 4
Fitzpatrick‐Schmidt, T., Dasa, V., Leonardi, C., Ferguson, T. F., Welsh, D. A., Molina, P. E., Ronis, M. J. J., & Edwards, S. (2025) · Journal of Pain · doi:10.1016/j.jpain.2025.105446 · Cited by 4
Self-citationPleasure Gone Awry? A New Conceptualization of Chronic Pain and Addiction
Hardcastle, V. G. (2013) · Review of Philosophy and Psychology · doi:10.1007/s13164-013-0170-3 · Cited by 4
Physiological Mechanisms Vulnerable to Alcohol‐Induced Alterations: Role in Chronic Comorbidities
Simon, L., Couvillion, K. E., Donovan, M. E., Gallegos, E. M., Souza‐Smith, F. M., & Molina, P. E. (2025) · Comprehensive physiology · doi:10.1002/cph4.70057 · Cited by 4
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816990-2.00001-6 · Cited by 4
Self-citationManaging Pain in Patients With Comorbid Alcohol Use Disorder and Chronic Pain
Maleki, N., Thompson, B., Janiuk, K., Dhingra, L. K., & Chen, L. L. (2024) · Current Addiction Reports · doi:10.1007/s40429-024-00563-1 · Cited by 3
Talani, G., Biggio, F., Mostallino, M. C., Batzu, E., Biggio, G., & Sanna, E. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110212 · Cited by 3
Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior
Higuera‐Matas, A., Miguéns, M., Olmo, N. D., Garcı́a-Lecumberri, C., & Ambrosio, E. (2011) · Pharmaceuticals · doi:10.3390/ph4101315 · Cited by 3
Neurobiological theories of addiction
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816863-9.00003-0 · Cited by 3
Self-citationBrouillette, A. E., & Edwards, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-26504-4.00018-1 · Cited by 1
Self-citationNeurobiología de la Patología Dual
Bernal, L. Á. R., & Pérez, G. A. C. (2017) · African journal of rhetoric · doi:10.21134/haaj.v17i2.310 · Cited by 2
Koob, G. F., Arends, M. A., McCracken, M. L., & Moal, M. L. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-816988-9.00001-1 · Cited by 2
Self-citationThe Role of Brain Glucocorticoid Systems in Alcohol Dependence
Whitaker, A. M., Priddy, B. M., Edwards, S., & Vendruscolo, L. F. (2016) · Neuropathology of Drug Addictions and Substance Misuse · doi:10.1016/b978-0-12-800213-1.00056-0 · Cited by 2
Self-citationBiological Mechanisms Underlying Addiction
Yargıç, İ. (2018) · International Journal of Human and Health Sciences (IJHHS) · doi:10.31344/ijhhs.v2i3.37 · Cited by 2
Assis, M. A., Díaz, D., Ferrado, R., Ávila-Zarza, C. A., Weruaga, E., & Ambrosio, E. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.11.039 · Cited by 3
The Interactional Approach in the Treatment of Cocaine Addicts
Leonardi, A., Scavelli, S., & Ciuffardi, G. (2012) · InTech eBooks · doi:10.5772/50728 · Cited by 1
Koob, G. F., Kandel, D. B., Baler, R., & Volkow, N. D. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_29 · Cited by 1
Self-citationFitzpatrick‐Schmidt, T., Mansouri, A., Adamec, J., Klein, J., Coleman, L., Edwards, K. N., Simon, L., Molina, P. E., Salling, M. C., & Edwards, S. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10179-5 · Cited by 1
Self-citationThe Problem of Outcomes in Addiction Treatments, the Inconvenient Truths
Mehendale, A. W., Goldman, M. P., Cizerle, K., & Parvin, T. L. (2016) · Journal of Addiction and Preventive Medicine · Cited by 1
Gendy, M. N. S. (2019) · TSpace (University of Toronto) · Cited by 1
Orexin Neural Activity Associated with Morphine Spontaneous Withdrawal-Induced Anxiety in Rats
Ly, R. (2011) · Digital Commons @ Connecticut College (Connecticut College)
Harrison, J. (2012) · eScholarship@McGill (McGill) · doi:10.82308/17878
1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Addiction: Experimental Studies
Antkiewicz‐Michaluk, L., & Michaluk, J. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1542-8_4
Corticotropin-Releasing Factor Signaling at the Intersection of Pain and Opioid Addiction
McGinn, M. A., & Edwards, S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800213-1.00083-3
Self-citationNikolaidou, M. (2015) · The University of Bath Online Publications Store (The University of Bath)
Circadian Mechanisms Underlying
Neurophysiology, R.-R., & McClung, C. A. (2016)
Motivating Change in Addiction via Modulation of the Dark Side
Koob, G. F. (2018) · Nebraska Symposium on Motivation/The Nebraska symposium on motivation · doi:10.1007/978-3-319-96920-6_1
Self-citationThe Neuropsychoendocrinology of Substance Use Disorders
Aoun, E. G., & Schmidt, K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-54856-4.00004-3
Abstinência à cocaína e suas consequências no sistema colinérgico muscarínico
Torres, Y. Y. S. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.9.2019.tde-29032019-095537
Campos‐Jurado, Y., Lorente, J. D., González-Romero, J. L., Granero, L. M., Polache, A., & Hipólito, L. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/862318
Assessment of Substance Use Disorders
Langenbucher, J. (2019) · The Cambridge Handbook of Clinical Assessment and Diagnosis · doi:10.1017/9781108235433.028 · Cited by 1
A VIVÊNCIA DA SEXUALIDADE NOS IDOSOS: UMA LEITURA HOLÍSTICA ATRAVÉS DA ENFERMAGEM
Júnior, R. D. M. F., Brandão, T. P., & dos Santos, A. J. (2021) · Editora Omnis Scietia eBooks · doi:10.47094/978-65-88958-33-9/216-226
Santiago, A. C. D. S., da Silva, M. L. F. I., Magalhães, L. M. V., Júnior, J. A. D. A., & Pereira, M. C. (2021) · Editora Omnis Scietia eBooks · doi:10.47094/978-65-88958-71-1/39-48
Brito, A. C. C. C., Muniz, L. S., Moreira, R. D. S., Costa, N. S. P., Santana, N., & de Barros, R. D. (2021) · Editora Omnis Scietia eBooks · doi:10.47094/978-65-88958-71-1/15-32
Reichert, R. A., Sales, D. A., Wisnieski, S. K. D. R., Frizzo, R. D. S., Stump, T. H., de MICHELI, D., de Oliveira, W. A., Pereira, F. A., Ramos, R. F. S., Preuhs, S. A., et al. (2021) · Editora Omnis Scietia eBooks · doi:10.47094/978-65-88958-71-1/177-198
External evidence against using less-than complete abstinence as a primary outcome in addiction
Kiran, T. (2019) · Addiction Research and Adolescent Behaviour · doi:10.31579/2688-7517/008
Lee, S., Fitzpatrick‐Schmidt, T., Bookman, D., & Edwards, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-34258-5.00008-6
Self-citationPhasic dopamine encodes persistent attraction to reward cuesPreprint
Townsend, E. S., Garrod, D., & Smith, K. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.09.693300
Prenatal Exposure to Low Alcohol and Alcohol Motivation in the Offspring
Pautassi, R. M., Fabio, M. C., & Sanchez, M. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-12741-9_4
Campos, R. C. (2017) · theses.fr (ABES) · doi:10.70675/03a75158z9d38z4e81zb3aczea487daa9f14
Shepherd, J. M., Rogers, A. H., Redmond, B. Y., Garey, L., Smit, T., Dietel, K., Bakhshaie, J., Lackner, J. M., & Zvolensky, M. J. (2026) · Journal of Behavioral Medicine · doi:10.1007/s10865-026-00700-3
Lavalley, C. A., Joshi, S., Kuplicki, R., Stewart, J. L., Choquette, E. M., Savitz, J. B., Paulus, M. P., & Aupperle, R. L. (2026) · NeuroImage Clinical · doi:10.1016/j.nicl.2026.104074
Metadata
- Authors
- Edwards, S., & Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Future Neurology
- Publisher
- Informa UK Limited
- Published
- 2010-05-05
- Volume
- 5
- Issue
- 3
- Pages
- 393-410
- ISSN
- 1479-6708 (ISSN-L)
- 1748-6971
- PMC
- PMC2886284
- OpenAlex
- W2163582947
- Semantic Scholar
- 543b3e9c9f2569f1549b9b9f2e206e9c70e83938
- Cited by
- 157
- References
- 184
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 11 · 2017: 14 · 2016: 14 · 2015: 8 · 2014: 8 · 2013: 14 · 2012: 9
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA008459, F32AA018250, P50AA006420, R37AA008459, P60AA006420)
- National Institute on Drug Abuse (R01DA010072, R01DA023597, R01DA004398, R01DA004043, R01DA023957)
- National Institute of Diabetes and Digestive and Kidney Diseases (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, motivation system, negative reinforcement, positive reinforcement, brain reward system, extended amygdala, stress system, compulsivity, drug-seeking behavior, drug use behavior, addiction treatment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
