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Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats.

Abstract

BACKGROUND AND PURPOSE

Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers.

EXPERIMENTAL APPROACH

Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex.

KEY RESULTS

THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA.

CONCLUSIONS AND IMPLICATIONS

Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs.

LINKED ARTICLES

This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.

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  • Authors+Show Affiliations

    ,

    Department of Animal Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.

    , ,

    Source

    British journal of pharmacology 171:6 2014 Mar pg 1435-47

    MeSH

    Adolescent
    Animals
    Calcium-Binding Proteins
    Cannabinoids
    Dronabinol
    Encephalitis
    Female
    Glial Fibrillary Acidic Protein
    Humans
    Male
    Microfilament Proteins
    N-Methyl-3,4-methylenedioxyamphetamine
    Rats
    Rats, Wistar
    Receptor, Cannabinoid, CB1
    Serotonin
    Sex Factors

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    24236988

    Citation

    Lopez-Rodriguez, Ana Belen, et al. "Sex-dependent Long-term Effects of Adolescent Exposure to THC And/or MDMA On Neuroinflammation and Serotoninergic and Cannabinoid Systems in Rats." British Journal of Pharmacology, vol. 171, no. 6, 2014, pp. 1435-47.
    Lopez-Rodriguez AB, Llorente-Berzal A, Garcia-Segura LM, et al. Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats. Br J Pharmacol. 2014;171(6):1435-47.
    Lopez-Rodriguez, A. B., Llorente-Berzal, A., Garcia-Segura, L. M., & Viveros, M. P. (2014). Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats. British Journal of Pharmacology, 171(6), pp. 1435-47. doi:10.1111/bph.12519.
    Lopez-Rodriguez AB, et al. Sex-dependent Long-term Effects of Adolescent Exposure to THC And/or MDMA On Neuroinflammation and Serotoninergic and Cannabinoid Systems in Rats. Br J Pharmacol. 2014;171(6):1435-47. PubMed PMID: 24236988.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats. AU - Lopez-Rodriguez,Ana Belen, AU - Llorente-Berzal,Alvaro, AU - Garcia-Segura,Luis M, AU - Viveros,Maria-Paz, PY - 2013/05/31/received PY - 2013/11/07/revised PY - 2013/11/13/accepted PY - 2013/11/19/entrez PY - 2013/11/19/pubmed PY - 2014/11/6/medline KW - CB1 receptor KW - MDMA KW - THC KW - adolescence KW - astrocytes KW - reactive microglia KW - serotonin transporter KW - sex differences SP - 1435 EP - 47 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 171 IS - 6 N2 - BACKGROUND AND PURPOSE: Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. EXPERIMENTAL APPROACH: Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. KEY RESULTS: THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. CONCLUSIONS AND IMPLICATIONS: Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. LINKED ARTICLES: This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/24236988/Sex_dependent_long_term_effects_of_adolescent_exposure_to_THC_and/or_MDMA_on_neuroinflammation_and_serotoninergic_and_cannabinoid_systems_in_rats_ L2 - https://doi.org/10.1111/bph.12519 DB - PRIME DP - Unbound Medicine ER -