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  • Reversal of Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area is Mediated by Protein Kinase C

    Author(s)
    Nimitvilai, Sudarat
    Arora, Devinder S
    Brodie, Mark S
    Griffith University Author(s)
    Arora, Devinder S.
    Year published
    2012
    Metadata
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    Abstract
    Adaptation of putative dopaminergic (pDA) neurons in the ventral tegmental area (VTA) to drugs of abuse may alter information processing related to reward and reinforcement and is an important factor in the development of addiction. We have demonstrated that prolonged increases in the concentration of dopamine (DA) result in a time-dependent decrease in sensitivity of pDA neurons to DA, which we termed DA inhibition reversal (DIR). In this study, we used extracellular recordings to examine factors mediating DIR. A 40?min administration of DA (2.5-10?卩, but not the DA D2 receptor agonist quinpirole (50-200?nM), resulted in ...
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    Adaptation of putative dopaminergic (pDA) neurons in the ventral tegmental area (VTA) to drugs of abuse may alter information processing related to reward and reinforcement and is an important factor in the development of addiction. We have demonstrated that prolonged increases in the concentration of dopamine (DA) result in a time-dependent decrease in sensitivity of pDA neurons to DA, which we termed DA inhibition reversal (DIR). In this study, we used extracellular recordings to examine factors mediating DIR. A 40?min administration of DA (2.5-10?卩, but not the DA D2 receptor agonist quinpirole (50-200?nM), resulted in inhibition of neuronal firing followed by DIR. In the presence of 100?nM cocaine, inhibition followed by DIR was seen with much lower DA concentrations. Reversal of quinpirole inhibition could be induced by an activator of protein kinase C, but not of protein kinase A. Inhibitors of protein kinase C or phospholipase C blocked the development of DIR. Disruption of intracellular calcium release also prevented DIR. Reduction of extracellular calcium or inhibition of store-operated calcium entry blocked DIR, but the L-type calcium channel blocker nifedipine did not. DIR was age-dependent and not seen in pDA VTA neurons from rat pups younger than 15 days postnatally. Our data indicate that DIR is mediated by protein kinase C, and implicate a conventional protein kinase C. This characterization of DIR gives insight into the regulation of autoinhibition of pDA VTA neurons, and the resulting long-term alteration in information processing related to reward and reinforcement.
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    Journal Title
    Neuropsychopharmacology
    Volume
    37
    DOI
    https://doi.org/10.1038/npp.2011.222
    Subject
    Biomedical and clinical sciences
    Central nervous system
    Psychology
    Publication URI
    http://hdl.handle.net/10072/52828
    Collection
    • Journal articles

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