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Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system
- Source :
- Journal of psychopharmacology (Oxford, England). 32(4)
- Publication Year :
- 2018
-
Abstract
- Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.
- Subjects :
- 0301 basic medicine
Male
Serotonin
Carbazoles
Pharmacology
Motor Activity
Serotonergic
Hippocampus
Indole Alkaloids
03 medical and health sciences
Mice
0302 clinical medicine
Neurotrophic factors
Fluoxetine
Medicine
Gemfibrozil
Animals
Pharmacology (medical)
RNA, Small Interfering
Cyclic AMP Response Element-Binding Protein
Oxazoles
Brain-derived neurotrophic factor
Membrane Glycoproteins
Behavior, Animal
Dose-Response Relationship, Drug
business.industry
Brain-Derived Neurotrophic Factor
Fenclonine
Immobility Response, Tonic
Protein-Tyrosine Kinases
Tail suspension test
Antidepressive Agents
Psychiatry and Mental health
030104 developmental biology
Antidepressant
Tyrosine
business
030217 neurology & neurosurgery
Behavioural despair test
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 14617285
- Volume :
- 32
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of psychopharmacology (Oxford, England)
- Accession number :
- edsair.doi.dedup.....5097e05f8c269f17b534ab7246db936b