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    Dopamine and stress system modulation of sex differences in decision making

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    Author
    Georgiou, P.
    Zanos, P.
    Bhat, S.
    Date
    2018
    Journal
    Neuropsychopharmacology
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1038/npp.2017.161
    Abstract
    Maladaptive decision making is associated with several neuropsychiatric disorders, including problem gambling and suicidal behavior. The prevalence of these disorders is higher in men vs women, suggesting gender-dependent regulation of their pathophysiology underpinnings. We assessed sex differences in decision making using the rat version of the Iowa gambling task. Female rats identified the most optimal choice from session 1, whereas male rats from session 5. Male, but not female rats, progressively improved their advantageous option responding and surpassed females. Estrus cycle phase did not affect decision making. To test whether pharmacological manipulations targeting the dopaminergic and stress systems affect decision making in a sex-dependent manner, male and female rats received injections of a dopamine D2 receptor (D2R) antagonist (eticlopride), D2R agonist (quinpirole), corticotropin-releasing factor 1 (CRF1) antagonist (antalarmin), and α2-adrenergic receptor antagonist (yohimbine; used as a pharmacological stressor). Alterations in mRNA levels of D2R and CRF1 were also assessed. Eticlopride decreased advantageous responding in male, but not female rats, whereas quinpirole decreased advantageous responding specifically in females. Yohimbine dose-dependently decreased advantageous responding in female rats, whereas decreased advantageous responding was only observed at higher doses in males. Antalarmin increased optimal choice responding only in female rats. Higher Drd2 and Crhr1 expression in the amygdala were observed in female vs male rats. Higher amygdalar Crhr1 expression was negatively correlated with advantageous responding specifically in females. This study demonstrates the relevance of dopaminergic- and stress-dependent sex differences to maladaptive decision making. Copyright 2018 American College of Neuropsychopharmacology.
    Sponsors
    This work was supported by Maryland Department of health and Mental Hygiene, Behavioral Health Administration, Grant # M00B4400404 and National Institute of Health 5R01MH091816.
    Keyword
    maladaptive decision making
    Brain Chemistry
    Decision Making
    Sex Factors
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046676895&doi=10.1038%2fnpp.2017.161&partnerID=40&md5=58c0f9ec5781b697ea86636935b3ef84; http://hdl.handle.net/10713/9267
    ae974a485f413a2113503eed53cd6c53
    10.1038/npp.2017.161
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