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Franceschelli THESIS__PDF_4-15-15 final format approved LW 4-15-15.pdf (677.7 KB)
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Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress
Author Info
Franceschelli, Anthony Albert
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481
Abstract Details
Year and Degree
2015, Master of Science (M.S.), University of Dayton, Biology.
Abstract
During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naive mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3 mg/kg at 30 min and 5 mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10 mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24 h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer-lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naive and CMS-exposed C57BL/6J mice.
Committee
Pothitos Pitychoutis, Dr. (Advisor)
Carissa Krane, Dr. (Committee Member)
Amit Singh, Dr. (Committee Member)
Pages
43 p.
Subject Headings
Behavioral Sciences
;
Biochemistry
;
Biology
;
Biomedical Research
;
Gender Studies
;
Neurobiology
;
Neurosciences
;
Pharmacology
Keywords
Ketamine
;
sex
;
gender
;
sex differences
;
chronic mild stress
;
mice
;
female
;
nmda
;
antidepressant
;
stress
;
chronic stress
;
chronic unpredictable stress
;
nmdar
;
gender differences
;
depression
;
major depression
;
major depressive disorder
;
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Citations
Franceschelli, A. A. (2015).
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress
[Master's thesis, University of Dayton]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481
APA Style (7th edition)
Franceschelli, Anthony.
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress.
2015. University of Dayton, Master's thesis.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481.
MLA Style (8th edition)
Franceschelli, Anthony. "Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress." Master's thesis, University of Dayton, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481
Chicago Manual of Style (17th edition)
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Document number:
dayton1429197481
Download Count:
1,190
Copyright Info
© 2015, all rights reserved.
This open access ETD is published by University of Dayton and OhioLINK.