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Using in Vivo Electrochemistry To Study the Physiological Effects of Cocaine and Other Stimulants on

Using in Vivo Electrochemistry To Study the Physiological Effects of Cocaine and Other Stimulants on

  1. Anonymous
    Makos et al
    ACS Chemical Neuroscience

    Dopamine neurotransmission is thought to play a
    critical role in addiction, reinforcing mechanisms of
    drugs of abuse. Electrochemical techniques have been
    employed extensively for monitoring in vivo dopamine
    changes in the brains of model organisms including
    rats, mice, and primates. Here, we investigated the
    effects of several stimulants on dopamine clearance
    using recently developed microanalytical tools for
    in vivo electrochemical measurements of dopamine in
    the central nervous system of Drosophila melanogaster.
    A cylindrical carbon-fiber microelectrode was placed
    in the protocerebral anterior medial region of the
    Drosophila brain (an area dense with dopamine neurons),
    while a micropipet injector was positioned to
    exogenously apply dopamine. Background-subtracted
    fast-scan cyclic voltammetry was carried out to quantify
    changes in dopamine concentration in the adult fly
    brain. Clearance of exogenously applied dopamine was
    significantly decreased in the protocerebral anterior
    medial area of the wild-type fly following treatment
    with cocaine, amphetamine, methamphetamine, or
    methylphenidate. In contrast, dopamine uptake remained
    unchanged when identical treatments were
    employed in fumin mutant flies that lack functional
    dopamine transporters. Our in vivo results support
    in vitro binding affinity studies predicting that these
    four stimulants effectively block normal Drosophila
    dopamine transporter function. Furthermore, we
    found 10 μM to be a sufficient physiological cocaine
    concentration to significantly alter dopamine transporter
    uptake in the Drosophila central nervous system.
    Taken together, these data indicate dopamine uptake
    in the Drosophila brain is decreased by psychostimulants
    as observed in mammals. This validates the use of
    Drosophila as a model system for future studies into the
    cellular and molecular mechanisms underlying drug
    addiction in humans.