An antisense oligonucleotide reverses the footshock-induced expression of Fos in the rat medial prefrontal cortex and the subsequent expression of conditioned fear-induced immobility

The immediate-early genes, including c-fos, have been proposed to be involv ed in learning and memory. In this report, we examine stress-induced Fos-li ke immunoreactivity (Fos-li) in subregions of the prefrontal cortex during a conditioned fear paradigm. During the acquisition phase, the rats were co nditioned to fear a formerly neutral tone by pairing the tone with a mild f ootshock. The rats were then tested for fearful behavior by reexposure to t he tone without additional footshock. During acquisition, Fos-li was increa sed in the medial prefrontal cortex (infralimbic and prelimbic) but not the anterior cingulate and M1 motor cortex. However, during the extinction pha se, no significant increase in Fos-li was observed in any region. These fin dings indicate that acquisition, but not extinction, of conditioned fear is associated with an increase in Fos-li in subregions of the medial prefront al cortex. In other animals, an antisense oligonucleotide directed against the c-fos mRNA was injected into the infralimbic/prelimbic cortex 12 or 72 hr before the acquisition session, Antisense treatment given 12, but not 72 , hr earlier suppressed Fos production without altering behavior during the acquisition session, Three days after the acquisition session, rats were t ested for fearful behavior as before, The antisense oligonucleotide blockad e of Fos production during acquisition was associated with a significantly less fearful response during the extinction session. These results support a role for Fos in the medial prefrontal cortex during the acquisition of av ersive learning.