Skip to Main Content
Frequently Asked Questions
Submit an ETD
Global Search Box
Need Help?
Keyword Search
Participating Institutions
Advanced Search
School Logo
Files
File List
19705.pdf (2.79 MB)
ETD Abstract Container
Abstract Header
MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity
Author Info
Huff, Courtney L., M.S.
ORCID® Identifier
http://orcid.org/0000-0002-0929-9016
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662
Abstract Details
Year and Degree
2016, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Abstract
MDMA is a unique psychostimulant that continues to be a popular drug of abuse. It is well documented that MDMA produces persistent reductions in markers of 5-HT axon terminals in rodents, as well as humans. To date, there has been little recognition of potential MDMA neurotoxicity to neuronal populations beyond 5-HT axon terminals in brain regions, such as the hippocampus, in which damage may account for the neurologic/cognitive effects associated with repeated exposure to MDMA. In the present study, we examined the hypothesis that MDMA produces glutamate-dependent damage to GABAergic neurons, as assessed from GAD67-positive neurons in the hippocampus, which results in an increase in seizure susceptibility. Repeated exposure to MDMA (3x10mg/kg, ip) resulted in a reduction of approximately 35- 55% in the number of GAD67 positive cells in the dentate gyrus, CA1, and CA3 regions. These reductions were significantly less in animals treated with MK-801 (an NMDA antagonist) or ceftriaxone (an inducer of GLT-1). In further support of overall hypothesis is the finding that MDMA increases the extracellular concentration of glutamate; this glutamate response was diminished in rats treated previously with either ceftriaxone or SC-51089 (a prostanoid EP1 receptor antagonist). Repeated administration of MDMA also resulted in an increased susceptibility to kainic acid-induced seizures that persisted for at least 30 days following MDMA treatment. Kainic acid (8 mg/kg, sc) produced seizures in approximately 20% of control animals, whereas approximately 85% of MDMA-treated animals exhibited kainic acid-induced seizures. The MDMA-induced increase in seizure susceptibility was not evident in rats treated with MK-801, ceftriaxone, or SC-51089. These findings substantiate a role for glutamate in the MDMA-induced damage to GABAergic neurons within the hippocampus and the subsequent increase in seizure susceptibility. Additional evidence is provided to support the hypothesis that prostaglandin signaling is necessary for the MDMA-induced increase in glutamate and the ultimate increase in seizure susceptibility.
Committee
Gary Gudelsky, Ph.D. (Committee Chair)
Steve Danzer, Ph.D. (Committee Member)
Jiukuan Hao, Ph.D. (Committee Member)
James Herman, Ph.D. (Committee Member)
Georg Weber, M.D. Ph.D. (Committee Member)
Pages
157 p.
Subject Headings
Pharmaceuticals
Keywords
MDMA
;
GABA
;
Neurotoxicity
;
Hippocampus
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
Huff, C. L. (2016).
MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity
[Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662
APA Style (7th edition)
Huff, Courtney.
MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity.
2016. University of Cincinnati, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662.
MLA Style (8th edition)
Huff, Courtney. "MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662
Chicago Manual of Style (17th edition)
Abstract Footer
Document number:
ucin1460444662
Download Count:
449
Copyright Info
© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.