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    Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

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    Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats (133.5Kb)

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    65
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    Author
    Adams, Cameron L.; Cowen, Michael S.; Short, Jennifer L.; Lawrence, Andrew J.
    Date
    2008
    Source Title
    International Journal of Neuropsychopharmacology
    Publisher
    Cambridge University Press
    University of Melbourne Author/s
    COWEN, MICHAEL; Lawrence, Andrew
    Affiliation
    Centre for Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Adams, C. L., Cowen, M. S., Short, J. L., & Lawrence, A. J. (2008). Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats. International Journal of Neuropsychopharmacology, 11(2), 229-241.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/32923
    DOI
    10.1017/S1461145707007845
    Description

    © 2010 CINP. Online edition of the journal is available at http://journals.cambridge.org/action/displayJournal?jid=PNP

    Abstract
    Adenosine and glutamate have been implicated as mediators involved in the self-administration of alcohol. In the present study we sought to determine whether adenosine receptors could interact with metabotropic glutamate receptors to regulate operant responding for alcohol and also the integration of the salience of alcohol-paired cues. Alcohol-preferring (iP) rats were trained to self-administer alcohol under operant conditions. The availability of alcohol was paired with an olfactory cue plus a stimulus light. Rats were examined under fixed ratio responding and also following extinction under a cue-induced reinstatement paradigm. Administration of the selective adenosine A2A receptor antagonist, SCH 58261, reduced fixed ratio responding for alcohol in iP rats in a dose-related manner. Furthermore, the combination of a subthreshold dose of SCH 58261 with a subthreshold dose of the mGlu5 receptor antagonist MTEP also reduced alcohol self-administration and increased the latency to the first reinforced response, suggesting a pre-ingestive effect. Moreover, this combination of SCH 58261 and MTEP also prevented the conditioned reinstatement of alcohol-seeking elicited by the re-presentation of cues previously paired with alcohol availability. In contrast, combinations of the selective adenosine A1 receptor antagonist, DPCPX, with either SCH 58261 or MTEP had no effect on alcohol responding. Collectively, these data suggest a functional interaction between adenosine A2A and mGlu5 receptors in relation to alcohol-seeking and the integration of the drug-related cues.
    Keywords
    adenosine A2A receptor; alcohol; glutamate mGlu5 receptor; reinstatement; self-administration

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