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Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus.

Abstract

Although Δ⁹-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ⁹-THC before and after inoculation with simian immunodeficiency virus (SIV(mac251), 100 TCID₅₀/ml, i.v.). Prior to chronic Δ⁹-THC and SIV inoculation, 0.032-0.32 mg/kg of Δ⁹-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ⁹-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7-12 months irrespective of SIV infection (i.e., +THC/-SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ⁹-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ⁹-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA. pwinsa@lsuhsc.edu

    , , , , , , , , , , ,

    Source

    MeSH

    Animals
    Behavior, Animal
    Blotting, Western
    Dronabinol
    Drug Tolerance
    Macaca mulatta
    Polymerase Chain Reaction
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Simian Acquired Immunodeficiency Syndrome
    Simian Immunodeficiency Virus

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    21463073

    Citation

    Winsauer, Peter J., et al. "Tolerance to Chronic Delta-9-tetrahydrocannabinol (Δ⁹-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus." Experimental and Clinical Psychopharmacology, vol. 19, no. 2, 2011, pp. 154-72.
    Winsauer PJ, Molina PE, Amedee AM, et al. Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus. Exp Clin Psychopharmacol. 2011;19(2):154-72.
    Winsauer, P. J., Molina, P. E., Amedee, A. M., Filipeanu, C. M., McGoey, R. R., Troxclair, D. A., ... Lewis, P. B. (2011). Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus. Experimental and Clinical Psychopharmacology, 19(2), pp. 154-72. doi:10.1037/a0023000.
    Winsauer PJ, et al. Tolerance to Chronic Delta-9-tetrahydrocannabinol (Δ⁹-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus. Exp Clin Psychopharmacol. 2011;19(2):154-72. PubMed PMID: 21463073.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus. AU - Winsauer,Peter J, AU - Molina,Patricia E, AU - Amedee,Angela M, AU - Filipeanu,Catalin M, AU - McGoey,Robin R, AU - Troxclair,Dana A, AU - Walker,Edith M, AU - Birke,Leslie L, AU - Stouwe,Curtis Vande, AU - Howard,Jessica M, AU - Leonard,Stuart T, AU - Moerschbaecher,Joseph M, AU - Lewis,Peter B, PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2011/7/23/medline SP - 154 EP - 72 JF - Experimental and clinical psychopharmacology JO - Exp Clin Psychopharmacol VL - 19 IS - 2 N2 - Although Δ⁹-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ⁹-THC before and after inoculation with simian immunodeficiency virus (SIV(mac251), 100 TCID₅₀/ml, i.v.). Prior to chronic Δ⁹-THC and SIV inoculation, 0.032-0.32 mg/kg of Δ⁹-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ⁹-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7-12 months irrespective of SIV infection (i.e., +THC/-SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ⁹-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ⁹-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. SN - 1936-2293 UR - https://www.unboundmedicine.com/medline/citation/21463073/abstract/Tolerance_to_chronic_delta_9_tetrahydrocannabinol__Δ⁹_THC__in_rhesus_macaques_infected_with_simian_immunodeficiency_virus_ L2 - http://content.apa.org/journals/pha/19/2/154 DB - PRIME DP - Unbound Medicine ER -