Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

Panayotis K. Thanos, Vanessa Gopez, Foteini Delis, Michael Michaelides, David Grandy, Gene Jack Wang, George Kunos, Nora D. Volkow

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Background: The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2.Methods: We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [3H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography.Results: We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake.Conclusions: The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

    Original languageEnglish (US)
    Pages (from-to)19-27
    Number of pages9
    JournalAlcoholism: Clinical and Experimental Research
    Volume35
    Issue number1
    DOIs
    StatePublished - Jan 2011

    Fingerprint

    Dopamine D2 Receptors
    Cannabinoids
    Knockout Mice
    Ethanol
    Up-Regulation
    rimonabant
    Locomotion
    Corpus Striatum
    Cannabinoid Receptor CB1
    Cannabinoid Receptors
    Caudate Nucleus
    Putamen
    Nucleus Accumbens
    Autoradiography
    Synaptic Transmission
    Cerebral Cortex
    Drinking
    Brain
    Water

    Keywords

    • Autoradiography
    • Cannabinoid
    • CB1
    • D2
    • Dopamine
    • Ethanol
    • Knockout

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Psychiatry and Mental health
    • Toxicology

    Cite this

    Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption. / Thanos, Panayotis K.; Gopez, Vanessa; Delis, Foteini; Michaelides, Michael; Grandy, David; Wang, Gene Jack; Kunos, George; Volkow, Nora D.

    In: Alcoholism: Clinical and Experimental Research, Vol. 35, No. 1, 01.2011, p. 19-27.

    Research output: Contribution to journalArticle

    Thanos, Panayotis K. ; Gopez, Vanessa ; Delis, Foteini ; Michaelides, Michael ; Grandy, David ; Wang, Gene Jack ; Kunos, George ; Volkow, Nora D. / Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption. In: Alcoholism: Clinical and Experimental Research. 2011 ; Vol. 35, No. 1. pp. 19-27.
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    AU - Michaelides, Michael

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    AU - Kunos, George

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