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The Neurobiology of Cocaine Addiction
Open accessAbstract
Cocaine produces its psychoactive and addictive effects primarily by acting on the brain's limbic system, a set of interconnected regions that regulate pleasure and motivation. An initial, short-term effect -- a buildup of the neurochemical dopamine -- gives rise to euphoria and a desire to take the drug again. Researchers are seeking to understand how cocaine's many longer term effects produce addiction's persistent cravings and risk of relapse. In the author's laboratory, work has focused on buildup of the genetic transcription factor DeltaFosB. Levels of DeltaFosB in the limbic system correlate with addiction-like behaviors in mice and may precipitate very long-lasting changes to nerve cell structure. Further pursuit of this and similar leads are first steps toward a complete understanding of the transition from cocaine abuse to addiction -- and, ultimately, more effective treatments for those who are addicted.
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“The induction of behavioral locomotor sensitization in response to cocaine depends on the structural plasticity of MSNs and is associated with lasting changes in MSN spine density32.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [32]
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“• Once created, a molecule of ΔFosB lasts for 6 to 8 weeks before breaking apart chemically (Nestler, Barrot, and Self, 2001).”
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Metadata
- Authors
- Nestler, E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Nestler, Eric
- ORCID
- Nestler, Eric
- Venue
- Science & Practice Perspectives
- Publisher
- NIDA/RTI International
- Published
- 2005-12
- Volume
- 3
- Issue
- 1
- Pages
- 4-10
- ISSN
- 1930-4307 (ISSN-L)
- 1930-4315
- PMC
- PMC2851032
- OpenAlex
- W2037400076
- Cited by
- 367
- References
- 11
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 31 · 2023: 25 · 2022: 17 · 2021: 28 · 2020: 67 · 2019: 19 · 2018: 18 · 2017: 6 · 2016: 22 · 2015: 19 · 2014: 10 · 2013: 13 · 2012: 17
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science & Practice Perspectives (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (K05 DA 00404, K05DA000404, P01DA08227, R37 DA 07359, R37DA007359, P01DA008227)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine dependence, limbic system, dopamine, ΔFosB, transcription factors, addiction-like behavior, relapse, neuroplasticity, drug craving, addiction treatment
- MeSH terms
- Gene Expression Regulation, Humans, Limbic System, Models, Neurological, Behavior, Addictive, Proto-Oncogene Proteins c-fos, Cocaine-Related Disorders
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