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    Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carbotplatin

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    Issue Date
    2015-06-15
    Author
    Kaplan, Sam V.
    Limbocker, Ryan A.
    Gehringer, Rachel C.
    Divis, Jenny L.
    Osterhaus, Gregory L.
    Newby, Maxwell D.
    Sofis, Michael J.
    Jarmolowicz, David P.
    Newman, Brooke D.
    Mathews, Tiffany A.
    Johnson, Michael A.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Rights
    This is an open access article published under an ACS AuthorChoice License at http://pubs.acs.org/page/policy/authorchoice_termsofuse.html , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
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    Abstract
    Chemotherapy-induced cognitive impairment, known also as “chemobrain”, is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional neurochemical and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced cognitive disorders.
    URI
    http://hdl.handle.net/1808/21107
    DOI
    https://doi.org/10.1021/acschemneuro.5b00029
    Collections
    • Applied Behavioral Science Scholarly Works [116]
    Citation
    Kaplan, S. V., Limbocker, R. A., Gehringer, R. C., Divis, J. L., Osterhaus, G. L., Newby, M. D., … Johnson, M. A. (2016). Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin. ACS Chemical Neuroscience, 7(6), 689–699. http://doi.org/10.1021/acschemneuro.5b00029

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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