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Neural and Behavioral Plasticity Associated with the Transition from Controlled to Escalated Cocaine Use

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Ferrario, Carrie R., Gorny, Grazyna, Crombag, Hans S., Li, Yilin, Kolb, Bryan, Robinson, Terry E.·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2005.04.046

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Abstract

Background Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction.Methods Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies.Results When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex).Conclusions The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.

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Authors: Ferrario, C. R., Gorny, G., Crombag, H. S., Li, Y., Kolb, B., & Robinson, T. E.
Affiliations: University of Michigan (US)
University of Lethbridge (CA)
Corresponding author: Robinson, Terry E.
ORCID: Ferrario, Carrie R.
Crombag, Hans S.
Li, Yilin
Kolb, Bryan
Robinson, Terry E.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2005-11
Volume: 58
Issue: 9
Pages: 751-759
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2005.04.046
OpenAlex: W2022992863
Cited by: 283
References: 58
Citations by year: 2026: 5 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 4 · 2021: 19 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 8 · 2016: 13 · 2015: 14 · 2014: 14 · 2013: 26 · 2012: 19
FWCI: 6.84
Type: journal article
Language: en
Open access: green
figshare.com
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Figshare (submittedVersion, cc-by)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: cocaine, extended access, restricted access, drug-seeking behavior, behavioral sensitization, nucleus accumbens core, dendritic spines, synaptic plasticity, addiction, locomotor sensitization, self-administration, extinction
MeSH terms: Animals, Behavior, Animal, Cocaine, Conditioning, Operant, Dendrites, Dose-Response Relationship, Drug, Male, Motor Activity, Neuronal Plasticity, Nucleus Accumbens, Reinforcement, Psychology, Self Administration, Stereotyped Behavior, Rats, Wistar, Prefrontal Cortex, Head Movements, Cocaine-Related Disorders, Rats

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Neural and Behavioral Plasticity Associated with the Transition from Controlled to Escalated Cocaine Use

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