Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF)

Wistar rats were kindled electrically in the anterior or posterior medial amygdala of the right hemisphere. One week after the fourth stage 5 seizure, anxiety was assessed in the elevated plus maze test. Anxiety levels of rats kindled in posterior medial amygdala were reduced relative to implanted controls, but not relative to unoperated controls. Kindling of the anterior medial amygdala increased anxiety relative to implanted and unoperated controls. The different effects of kindling on behavior were unrelated to any parameter of kindling. The stress of an ICV injection of saline increased anxiety in unkindled controls but reduced anxiety in anterior medial amygdala-kindled rats. Injection stress effects on behavior were blocked by 50 micrograms of alpha-helical CRF (the CRF receptor blocker). These findings suggest that CRF released by the stress of the injection procedure mediates the behavioral effects in both kindled and control rats. In contrast, injection of CRF (2 micrograms, ICV) has no greater effect than ICV saline in anterior medial amygdala kindled rats, whereas it was anxiogenic in unkindled rats. ICV vehicle and CRF reduce kindling-induced anxiety equally. These findings suggest that CRF released during the injection procedure saturates available CRF receptors. Finally, kindling did not alter basal plasma corticosterone levels. These and other findings suggest that the anxiety-modulating actions of CRF are at central CRF receptors.