Back to Search
Start Over
Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice
- Source :
- PLoS ONE, Vol 8, Iss 2, p e56053 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- BackgroundClinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK)-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS) mouse model of mice.Methodology/principal findingsAdult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days) group. Then, either vehicle, ketamine (10 mg/kg), or the established GSK-3 inhibitor, SB216763 (10 mg/kg), were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763). In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST) and forced swimming test (FST), the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed) mice.Conclusions/significanceThese findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice.
- Subjects :
- Male
Sucrose
Indoles
Mouse
Pharmacology
Open field
Maleimides
Glycogen Synthase Kinase 3
Mice
Behavioral Neuroscience
GSK-3
Molecular Cell Biology
Enzyme Inhibitors
health care economics and organizations
Psychiatry
Multidisciplinary
Behavior, Animal
Protein Kinase Signaling Cascade
Animal Models
Receptor antagonist
Antidepressive Agents
Signaling Cascades
Mental Health
Hindlimb Suspension
NMDA receptor
Antidepressant
Medicine
Ketamine
medicine.drug
Research Article
Signal Transduction
Drugs and Devices
Drug Research and Development
medicine.drug_class
Science
Motor Activity
Model Organisms
Stress, Physiological
medicine
Animals
Humans
Biology
Depressive Disorder
business.industry
Tail suspension test
Disease Models, Animal
Cellular Neuroscience
business
Behavioural despair test
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c01431d465af2b1825a4f90cbc3e99ac