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Antidepressant-like effect of nitric oxide synthase inhibitors and sildenafil against lipopolysaccharide-induced depressive-like behavior in mice
- Source :
- Neuroscience. 268:236-246
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Inflammation, oxidative and nitrosative stress underlie depression being assessed in rodents by the systemic administration of lipopolysacharide (LPS). There is an increasing body of evidence of an involvement of nitric oxide (NO) pathway in depression, but this issue was not investigated in LPS-induced model. Thus, herein we evaluated the effects of NO-pathway-modulating drugs, named aminoguanidine, l-NAME, sildenafil and l-arginine, on the behavioral (forced swimming test [FST], sucrose preference [SPT] and prepulse inhibition [PPI] of the startle) and neurochemical (glutathione [GSH], lipid peroxidation, IL-1β) alterations in the prefrontal cortex, hippocampus and striatum as well as in BDNF levels in the hippocampus 24h after LPS (0.5mg/kg, i.p.) administration, a time-point related to depressive-like behavior. Twenty-four hours post LPS there was an increase in immobility time in the FST, decrease in sucrose preference and PPI levels accompanied by a decrease in GSH levels and an increase in lipid peroxidation, IL-1β and hippocampal BDNF levels suggestive of a depressive-like state. The pretreatment with the NOS inhibitors, l-NAME and aminoguanidine as well as sildenafil prevented the behavioral and neurochemical alterations induced by LPS, although sildenafil and l-NAME were not able to prevent the increase in hippocampal BDNF levels induced by LPS. The iNOS inhibitor, aminoguanidine, and imipramine prevented all behavioral and neurochemical alterations induced by LPS. l-arginine did not prevent the alterations in immobility time, sucrose preference and GSH induced by LPS. Taken together our results show that the NO-cGMP pathway is important in the modulation of the depressive-like alterations induced by LPS.
- Subjects :
- Lipopolysaccharides
Male
Imipramine
medicine.medical_specialty
Interleukin-1beta
Arginine
Nitric Oxide
Guanidines
Piperazines
Sildenafil Citrate
Nitric oxide
Lipid peroxidation
Mice
chemistry.chemical_compound
Neurochemical
Internal medicine
medicine
Animals
Sulfones
Enzyme Inhibitors
Cyclic GMP
Brain-derived neurotrophic factor
Depressive Disorder
Behavior, Animal
biology
Chemistry
Brain-Derived Neurotrophic Factor
General Neuroscience
Brain
Antidepressive Agents
Nitric oxide synthase
Disease Models, Animal
Oxidative Stress
NG-Nitroarginine Methyl Ester
Endocrinology
Purines
biology.protein
TLR4
Nitric Oxide Synthase
Signal Transduction
Behavioural despair test
medicine.drug
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 268
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....3b62c8d70c03b78ac125bfcc4467d64d