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Research ArticleNEUROPHARMACOLOGY

Stress-Induced Suppression of the Immune System after Withdrawal from Chronic Cocaine

Albert H. Avila, Camille A. Morgan and Barbara M. Bayer
Journal of Pharmacology and Experimental Therapeutics April 2003, 305 (1) 290-297; DOI: https://doi.org/10.1124/jpet.102.045989
Albert H. Avila
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Camille A. Morgan
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Barbara M. Bayer
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Abstract

Recent evidence suggests that withdrawal from cocaine shares similarities to the stress response. Here, we examine whether withdrawal from chronic cocaine produces immune system alterations and whether the hypothalamic-pituitary-adrenal axis is involved. Sprague-Dawley male rats received cocaine (10 mg/kg i.p., b.i.d.) or saline, followed by 2 h, 1, 2, 4, 6, and 14 days of withdrawal. Proliferation responses of peripheral blood lymphocytes to concanavalin A were significantly suppressed at the 2-h, 1- and 2-day time points, and persisted for up to 6 days during withdrawal from chronic cocaine. Flow cytometric analysis revealed no significant differences in the immunophenotype of blood lymphocytic populations of T cells, B cells, or monocytes at 2 or 6 days of withdrawal from cocaine. Consistent with the suppression in cellular immunity observed in the in vitro response, the in vivo delayed-type hypersensitivity response was also significantly decreased in cocaine withdrawing animals. Plasma corticosterone levels were significantly elevated 2 and 24 h after cessation of cocaine but returned to basal values by 2 days of withdrawal. The suppressive effects of cocaine withdrawal were no longer observed in either adrenalectomized animals or those treated with the glucocorticoid receptor antagonist mifepristone (RU486), when administered during the first 2 days of withdrawal. These data argue that repeated exposure to cocaine followed by withdrawal leads to an activation of the neuroendocrine stress response, which alters cellular immunity during the initial withdrawal phase and may contribute to an increased susceptibility to infection.

Footnotes

  • This work was supported by National Institute on Drug Abuse Grants R01-DA04358 (to B.M.B.), National Institute on Drug Abuse Grants R01-DA11681 (to B.M.B.), and Training Grant from National Institute on Drug Abuse 5T53 DA07291.

  • DOI: 10.1124/jpet.102.045989

  • Abbreviations:
    CRF
    corticotropin-releasing factor
    HPA
    hypothalamic-pituitary-adrenal
    ACTH
    adrenocorticotropin
    WBC
    white blood cell
    FACs
    flow cytometric analysis
    PBS
    phosphate-buffered saline
    MoAb
    monoclonal antibody
    FITC
    fluorescein isothiocyanate
    BSA
    bovine serum albumin
    FCA
    Freund's complete adjuvant
    Con A
    concanavalin A
    ANOVA
    analysis of variance
    DTH
    delayed-type hypersensitivity
    IL
    interleukin
    wdl
    withdrawal
    CGP37849
    (E)-(±)-2-amino-4-methyl-5-phosphono-3-pentenoic acid
    • Received October 23, 2002.
    • Accepted January 7, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 305 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 305, Issue 1
1 Apr 2003
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Research ArticleNEUROPHARMACOLOGY

Stress-Induced Suppression of the Immune System after Withdrawal from Chronic Cocaine

Albert H. Avila, Camille A. Morgan and Barbara M. Bayer
Journal of Pharmacology and Experimental Therapeutics April 1, 2003, 305 (1) 290-297; DOI: https://doi.org/10.1124/jpet.102.045989

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Research ArticleNEUROPHARMACOLOGY

Stress-Induced Suppression of the Immune System after Withdrawal from Chronic Cocaine

Albert H. Avila, Camille A. Morgan and Barbara M. Bayer
Journal of Pharmacology and Experimental Therapeutics April 1, 2003, 305 (1) 290-297; DOI: https://doi.org/10.1124/jpet.102.045989
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