Related Experiment Video
Updated: Sep 27, 2026
Social Threat-Safety Test Uncovers Psychosocial Stress-Related Phenotypes
Published on: December 15, 2023
[Potential anxiolytic role of c-fos antisense oligonucleotide in social-defeated rats]
Objectives:
This study was to explore the therapeutic potential of c-fos antisense phosphorothioate oligonucleotide and the possible molecular mechanism.
Methods:
On the basis of the sequence of c-fos mRNA, two 15-mer phosphorothioated oligodeoxynucleotide(ODN) were synthesized. Antisense ODN was corresponded to the initiation codon of c-fos mRNA. The complementary sense and vehicle(saline) served as controls. Anxiety was induced in rats by a social-defeated paradigm and then rats were given a 5-minute exposure to the plus maze and open field test. Rats were injected c-fos antisense, sense ODNs and vehicles into the lateral ventricle through stainless-steel guide cannulate implanted unilaterally from the beginning of the experiment. The expression of the protein product of the immediate early gene c-fos was analyzed with immunochemistry in different brain regions, such as the amygdala and paraventricularis hypothalami nucleus. Computer assisted image analysis was performed to quantify the results of immuno-cytochemistry.
Results:
Socially defeated c-fos antisense-treated rats displayed obviously reduced anxiety-related behavior, as they spent significantly more time in the open arms of the plus maze compared to sense ODN- and vehicle-treated rats. The behavioral effects were similar to those of established anti-anxiety drugs(diazepam). Antisense oligodeoxynucleotide significantly decreased Fos positive nucleus in paraventricularis hypothalami nucleus. The inhibitory efficiency was 57.03%.
Conclusion:
Our data provide further evidence that c-fos is involved in acute stress elicited anxiety related behavior.
Insights
This study explored c-fos antisense phosphorothioate oligonucleotide as a potential anxiety treatment. Results show reduced anxiety-related behavior in rats, suggesting c-fos involvement in stress responses.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Context:
- Anxiety disorders are a significant public health concern.
- The immediate early gene c-fos plays a role in stress and anxiety.
- Developing novel therapeutic strategies for anxiety is crucial.
Purpose:
- To investigate the therapeutic potential of c-fos antisense phosphorothioate oligonucleotide.
- To elucidate the molecular mechanisms underlying c-fos in anxiety-related behavior.
Summary:
- Rats subjected to social defeat and treated with c-fos antisense oligodeoxynucleotide exhibited reduced anxiety-like behaviors.
- Treatment significantly decreased Fos-positive nuclei in the paraventricularis hypothalami nucleus.
- The observed behavioral effects were comparable to diazepam, a known anxiolytic.
Impact:
- Provides evidence for c-fos's role in acute stress-induced anxiety.
- Suggests c-fos antisense oligonucleotides as a potential therapeutic agent for anxiety.
- Opens avenues for further research into gene-targeted therapies for stress-related disorders.
