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Research ArticleArticle

Corticosterone Facilitates the Acquisition of Cocaine Self-Administration in Rats: Opposite Effects of the Type II Glucocorticoid Receptor Agonist Dexamethasone

John R. Mantsch, David Saphier and Nick E. Goeders
Journal of Pharmacology and Experimental Therapeutics October 1998, 287 (1) 72-80;
John R. Mantsch
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David Saphier
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Nick E. Goeders
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Abstract

The effect of corticosterone on the acquisition of cocaine-seeking behavior was investigated in rats using ascending dose-response curves for intravenous cocaine self-administration. Rats pretreated daily with corticosterone (2.0 mg/kg i.p.) acquired cocaine self-administration at a lower dose compared with vehicle-treated controls. In contrast, daily corticosterone pretreatment did not alter food-maintained responding. Cocaine self-administration was not affected by the type I (mineralocorticoid) receptor agonist, aldosterone (100 μg/kg). However, rats treated with the type II (glucocorticoid) receptor agonist, dexamethasone (10 or 100 μg/kg) did not acquire self-administration at any dose tested. The 100 μg/kg dose of dexamethasone attenuated food-reinforced behavior and decreased body weight, but these effects were not observed with the 10 μg/kg dose. Dexamethasone dose-dependently attenuated the plasma corticosterone response to self-administered infusions or intraperitoneal injections of cocaine, indicating that the ability of dexamethasone to block cocaine-induced corticosterone secretion may have contributed to its effects on self-administration. Administration of aldosterone (100 μg/kg) together with 10 μg/kg dexamethasone restored self-administration to the level of vehicle-treated rats, suggesting that type I receptor occupation by corticosterone may be required for the acquisition of this behavior. These results indicate that stress-induced corticosterone secretion may provide a substrate through which stressors interact with cocaine reinforcement. Additionally, the finding that dexamethasone blocks the acquisition of cocaine self-administration may be relevant to the development of novel approaches to the treatment of cocaine addiction.

Footnotes

  • Send reprint requests to: Nick E. Goeders, Ph.D., Department of Pharmacology & Therapeutics, LSU Medical Center, P.O. Box 33932, 1501 Kings Highway, Shreveport, LA 71130-3932. E-mail:ngoede{at}lsumc.edu

  • ↵1 This work was supported by United States Public Health Service Grants DA06013 and DA05836–01 from the National Institute on Drug Abuse.

  • Abbreviations:
    HPA
    hypothalamo-pituitary-adrenal
    CRF
    corticotropin releasing factor
    ACTH
    adrenocorticotropic hormone
    LR
    low responder
    HR
    high responder
    EFS
    electric footshock
    MR
    mineralocorticoid receptor
    GR
    glucocorticoid receptor
    VEH
    vehicle
    CORT
    corticosterone
    ALDO
    aldosterone
    DEX
    dexamethasone
    ANOVA
    analysis of variance
    DA
    dopamine
    • Received March 3, 1998.
    • Accepted May 18, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 287, Issue 1
1 Oct 1998
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Research ArticleArticle

Corticosterone Facilitates the Acquisition of Cocaine Self-Administration in Rats: Opposite Effects of the Type II Glucocorticoid Receptor Agonist Dexamethasone

John R. Mantsch, David Saphier and Nick E. Goeders
Journal of Pharmacology and Experimental Therapeutics October 1, 1998, 287 (1) 72-80;

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Research ArticleArticle

Corticosterone Facilitates the Acquisition of Cocaine Self-Administration in Rats: Opposite Effects of the Type II Glucocorticoid Receptor Agonist Dexamethasone

John R. Mantsch, David Saphier and Nick E. Goeders
Journal of Pharmacology and Experimental Therapeutics October 1, 1998, 287 (1) 72-80;
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