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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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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Cross-sensitization and the resulting hyper-responsivity of dopaminergic systems also occurs between drugs of abuse and stress at both behavioral and physiological levels.
“and drugs of abuse and stress (at both behavioral and physiological levels) (Cruz, Marin, Leão, & Planeta, 2011; Garcia-Keller et al., 2013; Piazza et al., 1990).”
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 Garcia-Keller et al., 2013
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Self-citation
- 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
- PMC
- PMC4356180
- 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
- bronze
- doi.org
- 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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