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Antidepressant-like effect of ascorbic acid is associated with the modulation of mammalian target of rapamycin pathway
- Source :
- Journal of Psychiatric Research. 48:16-24
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- The present study investigated the involvement of the PI3K, GSK-3β, heme oxygenase-1 (HO-1) and mTOR in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST). Male Swiss mice were pretreated with ascorbic acid (1 mg/kg, p.o.) or vehicle and 45 min after, LY294002 (10 μg/site, i.c.v., reversible PI3K inhibitor), rapamycin (0.2 nmol/site, i.c.v., selective mTOR inhibitor), zinc protoporphyrin (ZnPP – 10 ng/site, i.c.v., HO-1 inhibitor) or vehicle was administered. We also investigated the synergistic effect of ascorbic acid (0.1 mg/kg, p.o., sub-effective dose in the TST) with lithium chloride (10 mg/kg, p.o., non-selective GSK-3β inhibitor), AR-A014418 (0.01 μg/site, i.c.v., selective GSK-3β inhibitor) or cobalt protoporphyrin (CoPP – 0.01 μg/site, i.c.v., HO-1 inducer) in the TST. The antidepressant-like effect of ascorbic acid (1 mg/kg, p.o.) was prevented by the treatment of mice with LY294002, rapamycin or ZnPP. In addition, sub-effective doses of lithium chloride, AR-A014418 or CoPP, combined with a sub-effective dose of ascorbic acid produced a synergistic antidepressant-like effect. We also demonstrated that 1 h after its administration, ascorbic acid increased the phosphorylation of p70S6K and the immunocontent of PSD-95 in the hippocampus of mice. These results indicate that the antidepressant-like effect of ascorbic acid in the TST might be dependent on the activation of PI3K and mTOR, inhibition of GSK-3β as well as induction of HO-1, reinforcing the notion that these are important targets for antidepressant activity and contributing to better elucidate the mechanisms underlying the antidepressant-like effect of ascorbic acid.
- Subjects :
- Male
Poison control
Ascorbic Acid
Pharmacology
Hippocampus
Mice
chemistry.chemical_compound
Animals
Medicine
LY294002
Enzyme Inhibitors
Biological Psychiatry
PI3K/AKT/mTOR pathway
Sirolimus
Dose-Response Relationship, Drug
Depression
business.industry
TOR Serine-Threonine Kinases
Zinc protoporphyrin
Membrane Proteins
Drug Synergism
Immobility Response, Tonic
Ascorbic acid
COPP
Antidepressive Agents
Tail suspension test
Heme oxygenase
Disease Models, Animal
Psychiatry and Mental health
Gene Expression Regulation
Hindlimb Suspension
chemistry
Exploratory Behavior
business
Disks Large Homolog 4 Protein
Guanylate Kinases
Signal Transduction
Subjects
Details
- ISSN :
- 00223956
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Journal of Psychiatric Research
- Accession number :
- edsair.doi.dedup.....e248ed7316a259a052b05c94d5f4f3e6