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Impact of Self-Administered Cocaine and Cocaine Cues on Extracellular Dopamine in Mesolimbic and Sensorimotor Striatum in Rhesus Monkeys
Open accessAbstract
Studies were conducted to determine the impact of self-administered cocaine on extracellular striatal dopamine in four rhesus monkeys. The extent to which external cue conditioning contributed to the effects of cocaine and whether there is activation of striatal dopaminergic neurotransmission during drug-seeking behavior was also examined. Microdialysis measurements were made at 2 min intervals in sensorimotor (dorsolateral) and mesolimbic (central and ventromedial) striatum. A fixed-ratio schedule of reinforcement was used, with cocaine availability signaled by a visual cue. Studies examined the effects of cocaine or cocaine cues against a drug-free baseline. Large (fivefold to eightfold) increases in extracellular dopamine after a self-administered infusion of 0.5 mg/kg cocaine were quite rapid and matched the time course of reported subjective effects in human laboratory studies. To determine if conditioning to external cues contributed to the cocaine-induced increases, saline was substituted for cocaine in the infusion, leaving all other visual and auditory stimuli unchanged. No increase in extracellular dopamine in either sensorimotor or mesolimbic striatal subdivisions was observed. Extracellular dopamine during extended periods of drug-seeking behavior triggered by a visual cue was determined in both central and ventromedial striatum. This procedure also did not result in any measurable changes in extracellular dopamine. These studies demonstrate rapid and pronounced pharmacological actions of self-administered cocaine. No apparent conditioned component of those actions was associated with external environmental cues, suggesting that cues that trigger drug-seeking behavior in nonhuman primates do not cause conditioned increases in mesolimbic striatal dopamine.
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“Animal evidence suggests that the ability to increase dopamine in ventral striatum, involved with reward circuitry, is a common pharmacological effect underlying the reinforcing properties of virtually all drugs of abuse (Di Chiara and Imperato, 1988; Bradberry et al., 2000).”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Bradberry et al., 2000
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Metadata
- Authors
- Bradberry, C. W., Barrett-Larimore, R. L., Jatlow, P., & Rubino, S. R.
- Affiliations
- Yale University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-05-15
- Volume
- 20
- Issue
- 10
- Pages
- 3874-3883
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772692
- OpenAlex
- W1888424353
- Cited by
- 137
- References
- 66
- Citations by year
- 2025: 1 · 2021: 1 · 2019: 4 · 2018: 1 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institutes of Health (5p50da004060-13, 5r29da008073-02)
- National Institute on Drug Abuse (DA 10331, R01DA010331, DA04060, DA 08073)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cocaine self-administration, extracellular dopamine, sensorimotor striatum, cocaine cues, drug-seeking behavior, fixed-ratio schedules, rhesus monkeys, microdialysis, dopamine signaling
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Conditioning, Psychological, Corpus Striatum, Dopamine, Extracellular Space, Macaca mulatta, Magnetic Resonance Imaging, Male, Nucleus Accumbens, Self Administration, Microdialysis, Dopamine Uptake Inhibitors, Cocaine-Related Disorders
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