[Potential anxiolytic role of c-fos antisense oligonucleotide in social-defeated rats].
OBJECTIVE
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%.


CONCLUSIONS
Our data provide further evidence that c-fos is involved in acute stress elicited anxiety related behavior.
Lu
X H
XH
Mental Health Institute, Hunan Medical University, Changsha 410011.
Li
L J
LJ
Li
C Q
CQ
Luo
X G
XG
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000628:therapy; D015316:Genetic Therapy; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos