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Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats.

Abstract

Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.

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  • Authors+Show Affiliations

    ,

    School of Psychology, University of Sydney, Sydney, NSW 2006, Australia.

    , , ,

    Source

    Neuropharmacology 46:7 2004 Jun pg 954-65

    MeSH

    Animals
    Cannabinoids
    Cyclohexanols
    Fever
    Male
    Motor Activity
    N-Methyl-3,4-methylenedioxyamphetamine
    Piperidines
    Pyrazoles
    Rats
    Rats, Wistar
    Receptor, Cannabinoid, CB1
    Rimonabant
    Serotonin

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    15081792

    Citation

    Morley, Kirsten C., et al. "Cannabinoids Prevent the Acute Hyperthermia and Partially Protect Against the 5-HT Depleting Effects of MDMA ("Ecstasy") in Rats." Neuropharmacology, vol. 46, no. 7, 2004, pp. 954-65.
    Morley KC, Li KM, Hunt GE, et al. Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats. Neuropharmacology. 2004;46(7):954-65.
    Morley, K. C., Li, K. M., Hunt, G. E., Mallet, P. E., & McGregor, I. S. (2004). Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats. Neuropharmacology, 46(7), pp. 954-65.
    Morley KC, et al. Cannabinoids Prevent the Acute Hyperthermia and Partially Protect Against the 5-HT Depleting Effects of MDMA ("Ecstasy") in Rats. Neuropharmacology. 2004;46(7):954-65. PubMed PMID: 15081792.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats. AU - Morley,Kirsten C, AU - Li,Kong M, AU - Hunt,Glenn E, AU - Mallet,Paul E, AU - McGregor,Iain S, PY - 2003/08/21/received PY - 2003/12/15/revised PY - 2004/01/07/accepted PY - 2004/4/15/pubmed PY - 2004/6/30/medline PY - 2004/4/15/entrez SP - 954 EP - 65 JF - Neuropharmacology JO - Neuropharmacology VL - 46 IS - 7 N2 - Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/15081792/Cannabinoids_prevent_the_acute_hyperthermia_and_partially_protect_against_the_5_HT_depleting_effects_of_MDMA__"Ecstasy"__in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390804000127 DB - PRIME DP - Unbound Medicine ER -