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THC Prevents MDMA Neurotoxicity in Mice.

Abstract

The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4) were pretreated with THC (3 mg/kg x 4) at room (21 degrees C) and at warm (26 degrees C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1) receptor antagonist AM251 and the CB(2) receptor antagonist AM630, as well as in CB(1), CB(2) and CB(1)/CB(2) deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to attenuate neuroinflammation in this process.

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  • Authors+Show Affiliations

    ,

    Departament de Ciències Experimentals i de la Salut, Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu Fabra, Barcelona, Spain. clara.tourino@upf.edu

    ,

    Source

    PloS one 5:2 2010 Feb 10 pg e9143

    MeSH

    Animals
    Astrocytes
    Body Temperature
    Dronabinol
    Fever
    Hallucinogens
    Indoles
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Microglia
    N-Methyl-3,4-methylenedioxyamphetamine
    Neurotoxicity Syndromes
    Piperidines
    Psychotropic Drugs
    Pyrazoles
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Temperature

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20174577

    Citation

    Touriño, Clara, et al. "THC Prevents MDMA Neurotoxicity in Mice." PloS One, vol. 5, no. 2, 2010, pp. e9143.
    Touriño C, Zimmer A, Valverde O. THC Prevents MDMA Neurotoxicity in Mice. PLoS ONE. 2010;5(2):e9143.
    Touriño, C., Zimmer, A., & Valverde, O. (2010). THC Prevents MDMA Neurotoxicity in Mice. PloS One, 5(2), pp. e9143. doi:10.1371/journal.pone.0009143.
    Touriño C, Zimmer A, Valverde O. THC Prevents MDMA Neurotoxicity in Mice. PLoS ONE. 2010 Feb 10;5(2):e9143. PubMed PMID: 20174577.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - THC Prevents MDMA Neurotoxicity in Mice. AU - Touriño,Clara, AU - Zimmer,Andreas, AU - Valverde,Olga, Y1 - 2010/02/10/ PY - 2009/04/17/received PY - 2010/01/19/accepted PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/10/1/medline SP - e9143 EP - e9143 JF - PloS one JO - PLoS ONE VL - 5 IS - 2 N2 - The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4) were pretreated with THC (3 mg/kg x 4) at room (21 degrees C) and at warm (26 degrees C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1) receptor antagonist AM251 and the CB(2) receptor antagonist AM630, as well as in CB(1), CB(2) and CB(1)/CB(2) deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to attenuate neuroinflammation in this process. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/20174577/THC_Prevents_MDMA_Neurotoxicity_in_Mice_ L2 - http://dx.plos.org/10.1371/journal.pone.0009143 DB - PRIME DP - Unbound Medicine ER -