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  • Phorbol ester reduces ethanol excitation of dopaminergic neurons of the ventral tegmental area: Involvement of protein kinase C theta

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    Author(s)
    Nimitvilai, S
    Arora, DS
    You, C
    McElvain, M
    Brodie, MS
    Griffith University Author(s)
    Arora, Devinder S.
    Year published
    2013
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    Abstract
    Neurons of the ventral tegmental area (VTA) play a key role in the rewarding and reinforcing effects of drugs of abuse, including alcohol. Ethanol directly increases the firing rate of dopaminergic (DAergic) VTA neurons, but modulation of the firing rate of DAergic VTA neurons can be controlled by a number of factors, including some that are under the control of protein kinase C (PKC). Application of phorbol esters activates PKC and the present study assessed the effect of a phorbol ester, phorbol 12-myristate 13-acetate (PMA), on ethanol-induced excitation of DA VTA neurons. Ethanol-induced excitation of DAergic VTA neurons ...
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    Neurons of the ventral tegmental area (VTA) play a key role in the rewarding and reinforcing effects of drugs of abuse, including alcohol. Ethanol directly increases the firing rate of dopaminergic (DAergic) VTA neurons, but modulation of the firing rate of DAergic VTA neurons can be controlled by a number of factors, including some that are under the control of protein kinase C (PKC). Application of phorbol esters activates PKC and the present study assessed the effect of a phorbol ester, phorbol 12-myristate 13-acetate (PMA), on ethanol-induced excitation of DA VTA neurons. Ethanol-induced excitation of DAergic VTA neurons was reduced significantly in the presence of PMA. This action of PMA was antagonized by chelerythrine chloride, a non-selective antagonist of PKC, but not by moderate concentrations of antagonists of conventional PKC isoforms (G涹76 and G涹83). A PKC d/? inhibitor antagonized PMA-induced reduction of ethanol excitation. Since PKCd antagonist G涹83 did not antagonize the effect of PMA on ethanol excitation, the PMA reduction of ethanol excitation is most likely to be mediated by PKC?. Antagonists of intracellular calcium pathways were ineffective in antagonizing PMA action on ethanol excitation, consistent with the lack of calcium dependence of PKC?. In summary, ethanol-induced excitation of VTA neurons is attenuated in the presence of PMA, and this attenuation appears to be mediated by PKC?. This novel mechanism for interfering with ethanol activation of reward-related neurons could provide a new target for pharmacotherapy to ameliorate alcoholism.
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    Journal Title
    Frontiers in Integrative Neuroscience
    Volume
    7
    Issue
    96
    DOI
    https://doi.org/10.3389/fnint.2013.00096
    Copyright Statement
    © The Author(s) 2013. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this journal please refer to the journal’s website or contact the authors.
    Subject
    Neurosciences
    Central nervous system
    Cognitive and computational psychology
    Publication URI
    http://hdl.handle.net/10072/58265
    Collection
    • Journal articles

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