Cited by 92Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchStress Responses and Cortisol

Cross‐sensitization between cocaine and acute restraint stress is associated with sensitized dopamine but not glutamate release in the nucleus accumbens

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Garcia‐Keller, C., Martinez, S. A., Esparza, M. A., Bollati, F., Kalivas, P. W., Cancela, L. M.·2013·European Journal of Neuroscience

Abstract

Repeated administration of psychostimulant drugs or stress can elicit a sensitized response to the stimulating and reinforcing properties of the drug. Here we explore the mechanisms in the nucleus accumbens ( NA c) whereby an acute restraint stress augments the acute locomotor response to cocaine. This was accomplished by a combination of behavioral pharmacology, microdialysis measures of extracellular dopamine and glutamate, and Western blotting for GluR1 subunit of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ( AMPA ) glutamate receptor ( AMPAR ). A single exposure to restraint stress 3 weeks before testing revealed that enduring locomotor sensitization to cocaine was paralleled by an increase in extracellular dopamine in the core, but not the shell subcompartment, of the NA c. Wistar rats pre‐exposed to acute stress showed increased basal levels of glutamate in the core, but the increase in glutamate by acute cocaine was blunted. The alterations in extracellular glutamate seem to be relevant, as blocking AMPAR by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione microinjection into the core prevented both the behavioral cross‐sensitization and the augmented increase in cocaine‐induced extracellular dopamine. Further implicating glutamate, the locomotor response to AMPAR stimulation in the core was potentiated, but not in the shell of pre‐stressed animals, and this was accompanied by an increase in NA c GluR1 surface expression. This study provides evidence that the long‐term expression of restraint stress‐induced behavioral cross‐sensitization to cocaine recapitulates some mechanisms thought to underpin the sensitization induced by daily cocaine administration, and shows that long‐term neurobiological changes induced in the NA c by acute stress are consequential in the expression of cross‐sensitization to cocaine.

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Authors
Garcia‐Keller, C., Martinez, S. A., Esparza, M. A., Bollati, F., Kalivas, P. W., & Cancela, L. M.
Affiliations
  • IFEC‐CONICET Departamento de Farmacología Facultad de Ciencias Químicas Universidad Nacional de Córdoba Córdoba Argentina
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • Medical University of South Carolina (US)
Corresponding author
Cancela, L. M.
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2013-01-29
Volume
37
Issue
6
Pages
982-995
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W2036405095
Cited by
92
References
74
Citations by year
2026: 2 · 2025: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 46 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 2
FWCI
2.13
Type
journal article
Language
en
Open access
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
Funders
  • Consejo Nacional de Investigaciones Científicas y Técnicas
  • Ministerio de Ciencia, Tecnología e Innovación Productiva
  • National Institute on Drug Abuse (R01DA012513, P50DA015369, R01DA003906)
  • Fondo para la Investigación Científica y Tecnológica
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 › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
cocaine, restraint stress, cross-sensitization, locomotor sensitization, nucleus accumbens, dopamine release, glutamate release, AMPA receptors, GluR1, CNQX, cocaine-induced locomotor activity
MeSH terms
Central Nervous System Stimulants, Animals, Cocaine, Dopamine, Exocytosis, Locomotion, Male, Neurons, Nucleus Accumbens, Restraint, Physical, Stress, Psychological, Gene Expression, Rats, Wistar, Receptors, AMPA, Glutamic Acid, 6-Cyano-7-nitroquinoxaline-2,3-dione, Protein Transport, Rats, Central Nervous System Sensitization

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