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Interaction of Brain Derived Neurotrophic Factor and the HPA Axis Stress Response System with Neonatal d-Methamphetamine Induced Spatial Learning and Memory Deficits.

Brown-Strittholt, Carrie Ann
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116173412

Abstract Details

2005, PhD, University of Cincinnati, Medicine : Molecular and Developmental Biology.
Neonatal methamphetamine (MA) exposure P11-20 or P11-15 in rats is known to produce long-term spatial learning and memory deficits. However, little is known concerning the mechanism by which this results. Data from experiments exploring behavior indicate a role for neurotrophins and corticosterone (CORT) in learning and memory processes. It is hypothesized that neonatal MA alters levels of neurotrophins and/or alters the stress/CORT response resulting in impaired spatial learning and memory deficits in the Morris water maze (MWM). The current set of experiments explored first the levels of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) during the neonatal dosing period and in adulthood. Treatment effects were observed for BDNF P15. Sex differences in hippocampal and hypothalamic protein content for BDNF were found at P11; higher levels occurring in male pups. Sex differences in hippocampal protein content for NGF were found at P15 and sex differences in the hypothalamus were found at P68; higher levels in females at both ages. Behavioral tests in the MWM mimicked previous results demonstrating a clear MA-induced spatial learning deficit. Anxiety testing demonstrated more exploratory behavior in female animals. Secondly, pharmacological and surgical methods of corticosterone regulation were explored. Metyrapone (MET) injection and bilateral adrenalectomy (ADX) approaches were successful in the adult animal. Swimming ability was impaired only in ADX animals without CORT replacement. Zero maze data indicated increased activity among animals treated neonatally with MA 20 mg/kg. Trends were apparent among MWM data indicating a slight correction of the MA-induced learning and memory deficit when CORT levels were controlled; however, the MA effect was not clear among control animals to enable a definitive comparison. Overall results suggest a role for neurotrophins and CORT in the mechanism of MA’s effects on the developing brain but neither appears to be the sole source of insult.
Charles Vorhees (Advisor)
255 p.

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Citations

  • Brown-Strittholt, C. A. (2005). Interaction of Brain Derived Neurotrophic Factor and the HPA Axis Stress Response System with Neonatal d-Methamphetamine Induced Spatial Learning and Memory Deficits. [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116173412

    APA Style (7th edition)

  • Brown-Strittholt, Carrie. Interaction of Brain Derived Neurotrophic Factor and the HPA Axis Stress Response System with Neonatal d-Methamphetamine Induced Spatial Learning and Memory Deficits. . 2005. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116173412.

    MLA Style (8th edition)

  • Brown-Strittholt, Carrie. "Interaction of Brain Derived Neurotrophic Factor and the HPA Axis Stress Response System with Neonatal d-Methamphetamine Induced Spatial Learning and Memory Deficits. ." Doctoral dissertation, University of Cincinnati, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1116173412

    Chicago Manual of Style (17th edition)

ucin1116173412
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© 2005, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.
Release 3.2.12