Korean J Physiol Pharmacol.  2016 Jul;20(4):357-366. 10.4196/kjpp.2016.20.4.357.

Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder

• Lee B
• Sur B
• Yeom M
• Shim I
• Lee H
• Hahm DH

• KMID: 2371053
• DOI: http://doi.org/10.4196/kjpp.2016.20.4.357

Abstract

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1β, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

Keyword

Anxiety; Ibuprofen; Inflammation; Post-traumatic stress disorder; Single prolonged stress

MeSH Terms

Animals
Anxiety
Arm
Brain
Brain-Derived Neurotrophic Factor
Hippocampus
Humans
Ibuprofen*
Immunohistochemistry
Inflammation
Male
Models, Animal*
Necrosis
Rats*
Rats, Sprague-Dawley
Stress Disorders, Post-Traumatic*
Brain-Derived Neurotrophic Factor
Ibuprofen

Figure

• 

  Fig. 1 Experimental schedule used for developing SPS-induced anxiety-like behaviors and IBU treatment.Different groups of rats, with seven animals per group, were used for all experiments.

• 

  Fig. 2 The effects of IBU administration on body weights gain (A) and serum CORT levels (B) of rats exposed to SPS.*p<0.05, ***p<0.001 vs. SAL group; #p<0.05 vs. SPS group.

• 

  Fig. 3 The effects of IBU administration on the percentage of time spent in open arms (A), the numbers of entries into open and closed arms (B), and the anxiety index (C) in the EPM test following SPS.**p<0.01 vs. SAL group; #p<0.05 vs. SPS group.

• 

  Fig. 4 The effects of IBU administration on locomotion and exploratory behavior in the open-field test following SPS.Change of numbers of crossing in the central zone (A) and the time spent in central zone and peripheral zone (B). *p<0.05 vs. SAL group; #p<0.05 vs. SPS group.

• 

  Fig. 5 The effects of IBU administration on the mean number of TNF-α- and IL-1β-stained hippocampal areas after behavioral tests.Representative photographs (A) and the relative percentage values (B). Sections were cut coronally at 30 µm. Scale bar indicates 50 µm. *p<0.05 and **p<0.01 vs. SAL group; #p<0.05 vs. SPS group.

• 

  Fig. 6 The effects of IBU on expression of TNF-α and IL-1β mRNAs in rats with SPS-induced hippocampal impairment.PCR bands on an agarose gel (A) and their relative intensities. The expression of TNF-α (B) and IL-1β (C) mRNAs were normalized to that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA as an internal control. *p<0.05 vs. SAL group; #p<0.05 vs. SPS group.

• 

  Fig. 7 The effects of IBU administration on expression of BDNF mRNA in rats subjected to SPS for 14 consecutive days.PCR bands on an agarose gel (A) and their relative intensities (B). **p<0.01 vs. SAL group; #p<0.05 vs. SPS group.

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