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OtherANALGESIA AND DRUGS OF ABUSE

Chronic Exposure to Morphine Increases Corticosteroid-Binding Globulin

Bruce Nock, Michele Wich and Theodore J. Cicero
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1262-1268;
Bruce Nock
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Michele Wich
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Theodore J. Cicero
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Abstract

Although it appears that corticosterone may play an important role in determining vulnerability to drugs of abuse, few studies have examined drug effects on factors that affect corticosterone efficacy. Thus, studies were carried out to assess the effects of morphine on corticosteroid-binding globulin (CBG), the major glucocorticoid binder in blood. Since CBG-bound hormone is thought to be physiologically inactive, changes in CBG levels could affect corticosterone action independently of hormone levels per se. We found that morphine caused a marked naltrexone-preventable increase (≈160%) in CBG in adult male rats. Elevated levels were seen by three days and were maximal at seven days after morphine pellet (75 mg) implantation. CBG levels remained elevated while morphine was detectable in blood and returned toward normal as the drug cleared from the system. A single morphine pellet was sufficient to induce a marked increase in the concentration of CBG and two or more pellets caused maximal upregulation. Baseline and stress levels of total corticosterone (bound and unbound) were normal after chronic exposure to morphine. However, due to the elevated level of CBG, the amount of free, physiologically active hormone was dramatically reduced. These results suggest that morphine may exert potent effects on corticosterone action that are not revealed by measurement of corticosterone alone. Furthermore, the increase in CBG resulting from chronic exposure to morphine might contribute to the perpetuation of drug use and to adverse effects of drug exposure by impairing normal functions of corticosterone.

Footnotes

  • Send reprint requests to: Bruce Nock, Ph.D., Washington University School of Medicine, Department of Psychiatry, 4940 Children’s Place, St. Louis, MO 63110.

  • ↵1 This research was supported in part by USPHS Grants DA09344 (B.N.), DA03833 (T.J.C.) and DA09140 (T.J.C.) from the National Institute on Drug Abuse.

  • ↵2 Recipient of Research Scientist Development Award DA00157.

  • ↵3 Recipient of Research Scientist Award DA00095.

  • Abbreviations:
    ACTH
    adrenocorticotropic hormone
    AIDS
    acquired immunodeficiency syndrome
    CBG
    corticosteroid-binding globulin
    HIV
    human immunodeficiency virus
    RIA
    radioimmunoassay
    • Received January 27, 1997.
    • Accepted May 5, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 3
1 Sep 1997
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OtherANALGESIA AND DRUGS OF ABUSE

Chronic Exposure to Morphine Increases Corticosteroid-Binding Globulin

Bruce Nock, Michele Wich and Theodore J. Cicero
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1262-1268;

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OtherANALGESIA AND DRUGS OF ABUSE

Chronic Exposure to Morphine Increases Corticosteroid-Binding Globulin

Bruce Nock, Michele Wich and Theodore J. Cicero
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1262-1268;
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