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Research ArticleBehavioral Pharmacology

Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice

Sylvia Fitting, David L. Stevens, Fayez A. Khan, Krista L. Scoggins, Rachel M. Enga, Patrick M. Beardsley, Pamela E. Knapp, William L. Dewey and Kurt F. Hauser
Journal of Pharmacology and Experimental Therapeutics January 2016, 356 (1) 96-105; DOI: https://doi.org/10.1124/jpet.115.226407
Sylvia Fitting
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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David L. Stevens
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Fayez A. Khan
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Krista L. Scoggins
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Rachel M. Enga
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Patrick M. Beardsley
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Pamela E. Knapp
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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William L. Dewey
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Kurt F. Hauser
Department of Pharmacology and Toxicology (S.F., D.L.S., F.A.K., K.L.S., R.M.E., P.M.B., P.E.K., W.L.D., K.F.H.), Department of Anatomy and Neurobiology (P.E.K., K.F.H.), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia
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Abstract

Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1–related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)–inducible manner [Tat(+)], their Tat(−) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(−)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(−)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence.

Footnotes

    • Received June 9, 2015.
    • Accepted November 4, 2015.
  • ↵1 Current affiliation: Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [R01 DA018633, R01 DA033200, R01 DA024661, K02 DA027374, K99 DA033878].

  • dx.doi.org/10.1124/jpet.115.226407.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 356 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 356, Issue 1
1 Jan 2016
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Research ArticleBehavioral Pharmacology

Morphine Tolerance and Dependence in HIV Tat Transgenic Mice

Sylvia Fitting, David L. Stevens, Fayez A. Khan, Krista L. Scoggins, Rachel M. Enga, Patrick M. Beardsley, Pamela E. Knapp, William L. Dewey and Kurt F. Hauser
Journal of Pharmacology and Experimental Therapeutics January 1, 2016, 356 (1) 96-105; DOI: https://doi.org/10.1124/jpet.115.226407

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Research ArticleBehavioral Pharmacology

Morphine Tolerance and Dependence in HIV Tat Transgenic Mice

Sylvia Fitting, David L. Stevens, Fayez A. Khan, Krista L. Scoggins, Rachel M. Enga, Patrick M. Beardsley, Pamela E. Knapp, William L. Dewey and Kurt F. Hauser
Journal of Pharmacology and Experimental Therapeutics January 1, 2016, 356 (1) 96-105; DOI: https://doi.org/10.1124/jpet.115.226407
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