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Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.

Abstract

Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA.

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  • Authors+Show Affiliations

    ,

    Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003, USA. yshen@cns.umass.edu

    ,

    Source

    Neuropharmacology 61:8 2011 Dec pg 1183-92

    MeSH

    Adrenergic Uptake Inhibitors
    Age Factors
    Analysis of Variance
    Animals
    Animals, Newborn
    Behavior, Animal
    Body Temperature
    Body Weight
    Brain
    Disease Models, Animal
    Dronabinol
    Drug Administration Schedule
    Exploratory Behavior
    Fever
    Hydroxyindoleacetic Acid
    Interpersonal Relations
    Male
    N-Methyl-3,4-methylenedioxyamphetamine
    Neurotoxicity Syndromes
    Protein Binding
    Psychotropic Drugs
    Rats
    Rats, Sprague-Dawley
    Reaction Time
    Serotonin

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21763331

    Citation

    Shen, Erica Y., et al. "Chronic Administration of THC Prevents the Behavioral Effects of Intermittent Adolescent MDMA Administration and Attenuates MDMA-induced Hyperthermia and Neurotoxicity in Rats." Neuropharmacology, vol. 61, no. 8, 2011, pp. 1183-92.
    Shen EY, Ali SF, Meyer JS. Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. Neuropharmacology. 2011;61(8):1183-92.
    Shen, E. Y., Ali, S. F., & Meyer, J. S. (2011). Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. Neuropharmacology, 61(8), pp. 1183-92. doi:10.1016/j.neuropharm.2011.07.002.
    Shen EY, Ali SF, Meyer JS. Chronic Administration of THC Prevents the Behavioral Effects of Intermittent Adolescent MDMA Administration and Attenuates MDMA-induced Hyperthermia and Neurotoxicity in Rats. Neuropharmacology. 2011;61(8):1183-92. PubMed PMID: 21763331.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. AU - Shen,Erica Y, AU - Ali,Syed F, AU - Meyer,Jerrold S, Y1 - 2011/07/13/ PY - 2011/01/16/received PY - 2011/06/27/revised PY - 2011/07/01/accepted PY - 2011/7/19/entrez PY - 2011/7/19/pubmed PY - 2012/8/2/medline SP - 1183 EP - 92 JF - Neuropharmacology JO - Neuropharmacology VL - 61 IS - 8 N2 - Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/21763331/Chronic_administration_of_THC_prevents_the_behavioral_effects_of_intermittent_adolescent_MDMA_administration_and_attenuates_MDMA_induced_hyperthermia_and_neurotoxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(11)00278-4 DB - PRIME DP - Unbound Medicine ER -