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    mGlu5 receptor functional interactions and addiction

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    Author
    Brown, RM; Mustafa, S; Ayoub, MA; Dodd, PR; Pfleger, KDG; Lawrence, AJ
    Date
    2012-01-01
    Source Title
    FRONTIERS IN PHARMACOLOGY
    Publisher
    FRONTIERS MEDIA SA
    University of Melbourne Author/s
    Lawrence, Andrew; Brown, Robyn
    Affiliation
    Florey Department Of Neuroscience And Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Brown, R. M., Mustafa, S., Ayoub, M. A., Dodd, P. R., Pfleger, K. D. G. & Lawrence, A. J. (2012). mGlu5 receptor functional interactions and addiction. FRONTIERS IN PHARMACOLOGY, 3, https://doi.org/10.3389/fphar.2012.00084.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/33061
    DOI
    10.3389/fphar.2012.00084
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345582
    Description

    C5 - Other Refereed Contribution to Refereed Journals

    Abstract
    The idea of "receptor mosaics" is that proteins may form complex and dynamic networks with respect to time and composition. These have the potential to markedly expand the diversity and specificity of G protein-coupled receptors (GPCR) signaling, particularly in neural cells, where a few key receptors have been implicated in many neurological and psychiatric disorders, including addiction. Metabotropic glutamate type 5 receptors (mGlu5) can form complexes with other GPCRs, including adenosine A(2A) and dopamine D(2) receptors. mGlu5-containing complexes have been reported in the striatum, a brain region critical for mediating the rewarding and incentive motivational properties of drugs of abuse. mGlu5-containing complexes and/or downstream interactions between divergent receptors may play roles in addiction-relevant behaviors. Interactions between mGlu5 receptors and other GPCRs can regulate the rewarding and conditioned effects of drugs as well as drug-seeking behaviors. mGlu5 complexes may influence striatal function, including GABAergic output of striatopallidal neurons and glutamatergic input from corticostriatal afferents. Given their discrete localization, mGlu5-[non-mGlu5] receptor interactions and/or mGlu5-containing complexes may minimize off-target effects and thus provide a novel avenue for drug discovery. The therapeutic targeting of receptor-receptor functional interactions and/or receptor mosaics in a tissue specific or temporal manner (for example, a sub-population of receptors in a "pathological state") might reduce detrimental side effects that may otherwise impair vital brain functions.
    Keywords
    Pharmacology and Pharmaceutical Sciences not elsewhere classified; Health not elsewhere classified

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