Imaging trait anxiety in high anxiety F344 rats: Focus on the dorsomedial prefrontal cortex

Abstract

Functional magnetic resonance imaging (fMRI) has become an important method in clinical psychiatry research whereas there are still only few comparable preclinical investigations. Herein, we report that fMRI in rats can provide key information regarding brain areas underlying anxiety behavior. Perfusion as surrogate for neuronal activity was measured by means of arterial spin labeling-based fMRI in various brain areas of high anxiety F344 rats and control Sprague-Dawley rats. In one of these areas, the dorsomedial prefrontal cortex (dmPFC), c-Fos labeling was compared between these two strains with immunolabeling. The effects of a neurotoxic ibotenic acid lesion of the dmPFC in F344 rats were examined in a social approach-avoidance anxiety procedure and fMRI. Regional brain activity of high anxiety F344 rats was different in selective cortical and subcortical areas as compared to that of low anxiety Sprague-Dawley rats; the largest difference (i.e. hyperactivity) was measured in the dmPFC. Independently, c-Fos labeling confirmed that F344 rats show increased dmPFC activity. The functional role was confirmed by neurotoxic lesion of the dmPFC that reversed the high anxiety-like behavior and partially normalized the brain activity pattern of F344 rats. The current findings may have translational value as increased activity is reported in an equivalent cortical area in patients with social anxiety, suggesting that pharmacological or functional inhibition of activity in this brain area should be explored to alleviate social anxiety in patients.