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Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects.

Abstract

Adolescence is a critical phase of active brain development often characterized by the initiation of marijuana (Cannabis sativa) use. Limited information is known regarding the endogenous cannabinoid system of the adolescent brain as well as related neurotransmitters that appear sensitive to cannabis exposure. We recently observed that adult rats pre-exposed to Delta-9-tetrahydrocannabinol (THC) during adolescence self-administered higher amounts of heroin and had selective impairments of the enkephalin opioid system within the nucleus accumbens (NAc) implicated in reward-related behavior. To explore the ontogeny of the cannabinoid and opioid neuronal systems in association with adolescence THC exposure, rats were examined at different adolescent stages during an intermittent THC paradigm (1.5 mg/kg i.p. every third day) from postnatal days (PNDs) 28-49. Rat brains were examined 24 h after injection at PND 29 (early adolescence), PND 38 (mid adolescence) and PND 50 (late adolescence) and analyzed for endocannabinoids (anandamide and 2-arachidonoylglycerol), Met-enkephalin, cannabinoid CB(1) receptors and micro opioid receptors (microOR) in the NAc, caudate-putamen and prefrontal cortex (PFC). Of the markers studied, the endocannabinoid levels had the most robust alterations throughout adolescence and were specific to the PFC and NAc. Normal correlations between anandamide and 2-arachidonoylglycerol concentrations in the NAc (positive) and PFC (negative) were reversed by THC. Other significant THC-induced effects were confined to the NAc - increased anandamide, decreased Met-enkephalin and decreased microORs. These findings emphasize the dynamic nature of the mesocorticolimbic endocannabinoid system during adolescence and the selective mesocorticolimbic disturbance as a consequence of adolescent cannabis exposure.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

    , , , , , ,

    Source

    MeSH

    Animals
    Arachidonic Acids
    Cannabinoid Receptor Modulators
    Cerebral Cortex
    Chromatography, High Pressure Liquid
    Dronabinol
    Endocannabinoids
    Enkephalin, Methionine
    Glycerides
    Limbic System
    Male
    Mass Spectrometry
    Neostriatum
    Neural Pathways
    Nucleus Accumbens
    Opioid Peptides
    Polyunsaturated Alkamides
    Prefrontal Cortex
    Psychotropic Drugs
    Radioimmunoassay
    Rats
    Rats, Long-Evans
    Receptor, Cannabinoid, CB1
    Receptors, Opioid, mu

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18674887

    Citation

    Ellgren, M, et al. "Dynamic Changes of the Endogenous Cannabinoid and Opioid Mesocorticolimbic Systems During Adolescence: THC Effects." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 18, no. 11, 2008, pp. 826-34.
    Ellgren M, Artmann A, Tkalych O, et al. Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol. 2008;18(11):826-34.
    Ellgren, M., Artmann, A., Tkalych, O., Gupta, A., Hansen, H. S., Hansen, S. H., ... Hurd, Y. L. (2008). Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 18(11), pp. 826-34. doi:10.1016/j.euroneuro.2008.06.009.
    Ellgren M, et al. Dynamic Changes of the Endogenous Cannabinoid and Opioid Mesocorticolimbic Systems During Adolescence: THC Effects. Eur Neuropsychopharmacol. 2008;18(11):826-34. PubMed PMID: 18674887.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. AU - Ellgren,M, AU - Artmann,A, AU - Tkalych,O, AU - Gupta,A, AU - Hansen,H S, AU - Hansen,S H, AU - Devi,L A, AU - Hurd,Y L, PY - 2008/01/24/received PY - 2008/06/13/revised PY - 2008/06/24/accepted PY - 2008/8/5/pubmed PY - 2008/12/17/medline PY - 2008/8/5/entrez SP - 826 EP - 34 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 18 IS - 11 N2 - Adolescence is a critical phase of active brain development often characterized by the initiation of marijuana (Cannabis sativa) use. Limited information is known regarding the endogenous cannabinoid system of the adolescent brain as well as related neurotransmitters that appear sensitive to cannabis exposure. We recently observed that adult rats pre-exposed to Delta-9-tetrahydrocannabinol (THC) during adolescence self-administered higher amounts of heroin and had selective impairments of the enkephalin opioid system within the nucleus accumbens (NAc) implicated in reward-related behavior. To explore the ontogeny of the cannabinoid and opioid neuronal systems in association with adolescence THC exposure, rats were examined at different adolescent stages during an intermittent THC paradigm (1.5 mg/kg i.p. every third day) from postnatal days (PNDs) 28-49. Rat brains were examined 24 h after injection at PND 29 (early adolescence), PND 38 (mid adolescence) and PND 50 (late adolescence) and analyzed for endocannabinoids (anandamide and 2-arachidonoylglycerol), Met-enkephalin, cannabinoid CB(1) receptors and micro opioid receptors (microOR) in the NAc, caudate-putamen and prefrontal cortex (PFC). Of the markers studied, the endocannabinoid levels had the most robust alterations throughout adolescence and were specific to the PFC and NAc. Normal correlations between anandamide and 2-arachidonoylglycerol concentrations in the NAc (positive) and PFC (negative) were reversed by THC. Other significant THC-induced effects were confined to the NAc - increased anandamide, decreased Met-enkephalin and decreased microORs. These findings emphasize the dynamic nature of the mesocorticolimbic endocannabinoid system during adolescence and the selective mesocorticolimbic disturbance as a consequence of adolescent cannabis exposure. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/18674887/Dynamic_changes_of_the_endogenous_cannabinoid_and_opioid_mesocorticolimbic_systems_during_adolescence:_THC_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(08)00170-3 DB - PRIME DP - Unbound Medicine ER -