Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests
-
Hossein Omidi-Ardali
Abstract
Objectives
Previous studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).
Methods
The antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.
Results
Findings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.
Conclusions
Our findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.
Funding source: Shahrekord University of Medical Sciences
Award Identifier / Grant number: 2134
Acknowledgments
The authors would like to thank Dr. Mahmoud Rafieian kopaei, Dr. Mohammad Reza Hojjati, and Mrs. Elham Bijad for their collaboration on this study.
Research funding: This work was supported by a grant from Shahrekord University of Medical Sciences (SKUMS) with grant number of “3556”.
Author contributions: H. O-A: performed experiments and writing the manuscript; A. G B: performed experiments; E. S: writing the manuscript and data analysis; M. S-K: data analysis and editing the manuscript H. A-K: study design, writing the manuscript.
Competing interests: The authors declare no conflicts of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: All procedures were performed in accordance with the National Institutes of Health (NIH) Guideline for the Care and Use of Laboratory Animals (NIH publication #80-23) and institutional guidelines for animal care and use (Shahrekord University of Medical Sciences, SKUMS) with ethical code number: IR.SKUMS.REC.1396. 223.
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© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Update of hypothyroidism and its management in Unani medicine
- Original Articles
- 6-OHDA mediated neurotoxicity in SH-SY5Y cellular model of Parkinson disease suppressed by pretreatment with hesperidin through activating L-type calcium channels
- Modulation of sleep using electrical vestibular nerve stimulation prior to sleep onset: a pilot study
- Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests
- Effect of mobile phone usage on cognitive functions, sleep pattern, visuospatial ability in Parkinsons patients; a possible correlation with onset of clinical symptoms
- Food-added azodicarbonamide alters haematogical parameters, antioxidant status and biochemical/histomorphological indices of liver and kidney injury in rats
- Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes
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- In vitro antioxidants and hepatoprotective effects of Pleurotus tuber-regium on carbon tetrachloride–treated rats
- Mitigative effect of Momordica cymbalaria fruit extract against sodium fluoride induced hepatotoxicity in Wistar male albino rats
- Amine-modified kaolinite clay preserved thyroid function and renal oxidative balance after sub-acute exposure in rats
- Aqueous extract of dry powder blend of seeds and leaves of Picralima nitida (Stapf) T. & H. Durand reduce pain and inflammation in animal models
- Methanol extract of Caesalpinia benthamiana normalizes blood pressure and attenuates oxidative stress in uninephrectomized hypertensive rats
- Evaluation of antidiabetic effect of Cistus salviifolius L. (Cistaceae) in streptozotocin-nicotinamide induced diabetic mice
- Correlation between biofilm formation and antimicrobial susceptibility pattern toward extended spectrum β-lactamase (ESBL)- and non-ESBL-producing uropathogenic bacteria
Articles in the same Issue
- Frontmatter
- Review
- Update of hypothyroidism and its management in Unani medicine
- Original Articles
- 6-OHDA mediated neurotoxicity in SH-SY5Y cellular model of Parkinson disease suppressed by pretreatment with hesperidin through activating L-type calcium channels
- Modulation of sleep using electrical vestibular nerve stimulation prior to sleep onset: a pilot study
- Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests
- Effect of mobile phone usage on cognitive functions, sleep pattern, visuospatial ability in Parkinsons patients; a possible correlation with onset of clinical symptoms
- Food-added azodicarbonamide alters haematogical parameters, antioxidant status and biochemical/histomorphological indices of liver and kidney injury in rats
- Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes
- p53 upregulated mediator of apoptosis (Puma) deficiency increases survival of adult neural stem cells generated physiologically in the hippocampus, but does not protect stem cells generated in surplus after an excitotoxic lesion
- In vitro antioxidants and hepatoprotective effects of Pleurotus tuber-regium on carbon tetrachloride–treated rats
- Mitigative effect of Momordica cymbalaria fruit extract against sodium fluoride induced hepatotoxicity in Wistar male albino rats
- Amine-modified kaolinite clay preserved thyroid function and renal oxidative balance after sub-acute exposure in rats
- Aqueous extract of dry powder blend of seeds and leaves of Picralima nitida (Stapf) T. & H. Durand reduce pain and inflammation in animal models
- Methanol extract of Caesalpinia benthamiana normalizes blood pressure and attenuates oxidative stress in uninephrectomized hypertensive rats
- Evaluation of antidiabetic effect of Cistus salviifolius L. (Cistaceae) in streptozotocin-nicotinamide induced diabetic mice
- Correlation between biofilm formation and antimicrobial susceptibility pattern toward extended spectrum β-lactamase (ESBL)- and non-ESBL-producing uropathogenic bacteria
