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    Involvement of Regulator of G-protein Signaling 9-2 in estrogenic augmentation of reward behavior

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    Author
    Silverman, Jill Lynn
    Advisor
    Koenig, James I.
    Date
    2007
    Type
    dissertation
    
    Metadata
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    Abstract
    Research indicates the gonadal hormone 17-beta estradiol enhances dopamine-mediated behaviors, which makes women and female rats more sensitive to the effects of the psychostimulant drug, amphetamine. Therefore, a strong emphasis has been placed on the effect of estradiol in the mesolimbic dopamine pathway. The studies described herein provided an analysis on a novel protein family termed the Regulators of G-protein Signaling (RGS) proteins. Preliminary data analyzed the effects of estradiol treatment and amphetamine administration on the expression of RGS9-2, RGS4 and RGS2 mRNA by employing ovariectomized female rats replaced with 17-beta estradiol by either Silastic implant (5-mm) or daily subcutaneous injections (80 mug/kg). After determining estradiol did indeed reduce the mRNA and protein expression of RGS9-2 we explored estradiol mediated enhanced amphetamine-induced conditioned place preference behavior (1.0 mg/kg). Enhanced amphetamine-induced place preference was observed and associated with reductions in RGS9-2 protein expression. Next, in order to demonstrate the direct interaction of the estradiol mediated enhanced place preference behavior and reductions in RGS9-2 we employed the well-established methodology of viral mediated transgene overexpression by herpes simplex virus (HSV) vectors. Overexpression of RGS9-2 in the nucleus accumbens shell by microinjection of HSV successfully increased the expression of RGS9-2 in the nucleus accumbens of treated rats and reversed the estradiol enhancement of amphetamine-induced place preference. The final series of experiments investigated the impact of a single microinjection of saline or pertussis toxin, which depletes Galphai, in the nucleus accumbens shell on estradiol-potentiated place preference behavior and RGS9-2 expression. In summary, twenty years of research involving estradiol enhancements of dopamine-mediated behaviors have been repeatedly reported. Yet, these studies are ambiguous regarding the involvement of dopamine and its receptors. The current research has investigated a novel mechanism by which estradiol may be acting to enhance behavior. The data that are complied in this dissertation demonstrate that reductions in RGS9-2 expression may underlie the mechanism of estradiol enhanced behavior. Thus, providing a great deal of evidence for its role in augmented behavioral responses that might be related to the enhanced susceptibility of addictive behavior in women.
    Description
    University of Maryland, Baltimore. Neuroscience. Ph.D. 2007
    Keyword
    Biology, Neuroscience
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1030
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