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Cited by 70Neurotransmitter Receptor Influence on BehaviorRedox biology and oxidative stressParkinson's Disease Mechanisms and Treatments

Involvement of reactive oxygen species in cocaine‐taking behaviors in rats

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Jang, Eun Young, Ryu, Yeon‐Hee, Lee, Bong Hyo, Chang, Su‐Chan, Yeo, Mi Jin, Kim, Sang Hyun, Folsom, Ryan J., Schilaty, Nathan D. +4 more·2015·Addiction Biology
DOI 10.1111/adb.12159PMC PMC4843775
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Abstract

Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self‐administration behavior, cocaine‐induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N‐tert‐butyl‐α‐phenylnitrone (PBN) or 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPOL), either pre‐ or post‐treatment, significantly decreased cocaine self‐administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self‐administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self‐administering cocaine.TEMPOL significantly attenuated cocaine‐induced enhancement of DA release in the NAc, compared to saline controls.TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR 12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine.

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Cited by

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Authors
Jang, E. Y., Ryu, Y., Lee, B. H., Chang, S., Yeo, M. J., Kim, S. H., Folsom, R. J., Schilaty, N. D., Kim, K. J., Yang, C. H., Steffensen, S. C., & Kim, H. Y.
Affiliations
  • Brigham Young University (US)
  • Acupuncture, Moxibustion & Meridian Research Center Division of Standard Research Korea Institute of Oriental Medicine South Korea
  • Daegu Haany University (KR)
  • College of Korean Medicine Daegu Haany University South Korea
Corresponding author
  • Steffensen, Scott C.
  • Kim, Hee Young
ORCID
Venue
Addiction Biology
Publisher
Wiley
Published
2014-06-26
Volume
20
Issue
4
Pages
663-675
ISSN
  • 1355-6215 (ISSN-L)
  • 1369-1600
DOI
10.1111/adb.12159
PMC
PMC4843775
OpenAlex
W1775287346
Cited by
70
References
2
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 12 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 5
FWCI
2.52
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Addiction Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Korea Institute of Oriental Medicine (K13290)
  • National Research Foundation of Korea (NRF)
  • Korea government MSIP (2011-0030124)
  • MEST (2011-0016038)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
reactive oxygen species, cocaine self-administration, nucleus accumbens, mesolimbic dopamine system, oxidative stress, tempol, PBN, dopamine release, cocaine reinforcement, brain metabolism
MeSH terms
Animals, Antioxidants, Cocaine, Conditioning, Operant, Cyclic N-Oxides, Dopamine, Male, Nucleus Accumbens, Piperazines, Reinforcement Schedule, Self Administration, Spin Labels, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Neuroprotective Agents, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Dopaminergic Neurons

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