Hippocampal involvement in the expression of kindling-induced fear in rats

Kindling dramatically increases fearful behavior in rats. Because kindling-induced fear increases in magnitude as rats receive more stimulations, kindling provides a superb opportunity to study the nature and neural mechanisms of fear sensitization. Interestingly, these changes in behavior are accompanied by increased binding to inhibitory receptors and decreased binding to excitatory receptors in the CA1 and dentate gyrus regions of the hippocampus. This led us to hypothesize that kindling-induced fear may result from an increased inhibitory tone within hippocampal circuits. To test this hypothesis, we investigated FOS protein immunoreactivity in hippocampal and amygdalar regions of kindled rats that were exposed to an unfamiliar open field. We found that FOS immunoreactivity was significantly decreased in the CA1 region, dentate gyrus, and perirhinal cortex of kindled rats compared to sham-stimulated rats. These results support our hypothesis that kindling-induced fear may be produced by inhibition within hippocampal circuits. They also suggest that neural changes within the hippocampus may be important for the sensitization of fear.