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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.
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“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]
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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
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