Neural and Behavioral Plasticity Associated with the Transition from Controlled to Escalated Cocaine Use
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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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This increased urge for the drug is due to a sensitization of the neural pathways responsible for 'wanting'.
“This increased urge for the drug is due to a sensitization of the neural pathways responsible for ‘wanting’ (Ferrario & Robinson, 2007; Ferrario et al., 2005).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Ferrario et al., 2005
Sensitization can be seen as a greater behavioral response to the drug or enhanced acquisition and escalation of drug self-administration, that accompany brain neural adaptations that underlie amplified 'wanting' for the reward.
“Sensitization can also be seen as a greater behavioral response to the drug or enhanced acquisition and escalation of drug self-administration, that accompany brain neural adaptations that underlie amplified ‘wanting’ for the reward (Ferrario et al., 2005; Ferrario & Robinson, 2007; Vezina, 2004; Vezina et al., 2002).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Ferrario et al., 2005
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Dopamine ‘ups and downs’ in addiction revisited
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Cocaine self-administration produces a persistent increase in dopamine D2High receptors
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“This increased urge for the drug is due to a sensitization of the neural pathways responsible for Bwanting^ (Ferrario & Robinson, 2007; Ferrario et al., 2005).”
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Motivational Processes Underlying Substance Abuse Disorder
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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.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 58
- Issue
- 9
- Pages
- 751-759
- ISSN
- 0006-3223 (ISSN-L)
- 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
- 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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