Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress
| Main Author: | |
|---|---|
| Language: | English |
| Published: |
University of Dayton / OhioLINK
2015
|
| Subjects: | |
| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481 |
| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-dayton1429197481 |
|---|---|
| record_format |
oai_dc |
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-dayton14291974812021-08-03T06:30:16Z Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress Franceschelli, Anthony Albert Biology Biomedical Research Behavioral Sciences Biochemistry Gender Studies Neurobiology Neurosciences Pharmacology 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 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. 2015-05-27 English text University of Dayton / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481 http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biology Biomedical Research Behavioral Sciences Biochemistry Gender Studies Neurobiology Neurosciences Pharmacology 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 |
| spellingShingle |
Biology Biomedical Research Behavioral Sciences Biochemistry Gender Studies Neurobiology Neurosciences Pharmacology 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 Franceschelli, Anthony Albert 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 |
Franceschelli, Anthony Albert |
| author_facet |
Franceschelli, Anthony Albert |
| author_sort |
Franceschelli, Anthony Albert |
| title |
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress |
| title_short |
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress |
| title_full |
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress |
| title_fullStr |
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress |
| title_full_unstemmed |
Sex Differences in the Rapid and the Sustained Antidepressant-like Effects of Ketamine in Stress-naive and “Depressed” Mice Exposed to Chronic Mild Stress |
| title_sort |
sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naive and “depressed” mice exposed to chronic mild stress |
| publisher |
University of Dayton / OhioLINK |
| publishDate |
2015 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=dayton1429197481 |
| work_keys_str_mv |
AT franceschellianthonyalbert sexdifferencesintherapidandthesustainedantidepressantlikeeffectsofketamineinstressnaiveanddepressedmiceexposedtochronicmildstress |
| _version_ |
1719437851511226368 |