The amygdala-kindling model is often used as an animal model of epileptogenesis; however, it has also proven useful for studying fear sensitization, as a model of interictal (i.e., between seizure) anxiety. The expression of fearful behaviour has been well characterized in kindled male rats but not in females. Furthermore, the neural mechanisms underlying kindled fear is not fully understood. Consequently, sex differences and the neural mechanisms of kindled fear are addressed in this thesis. In Experiment 1, kindled males and females are compared on several measures of fearfulness and found to exhibit similar levels of kindled fear. In Experiment 2, the hypothesis that kindled fear is associated with hippocampal-dependent dysfunction was tested. This was found to be true, particularly for kindled males. The results of Experiment 2 also indicated that the kindled females that were exposed to the hippocampal-dependent test showed reduced fear compared to those that were not exposed to the task. In Experiment 3, the role of hippocampal cell proliferation was examined in relation to kindled fear. The results showed that cell proliferation was elevated prior to the manifestation of kindled fear, suggesting that it could contribute the development of kindled fear. In Experiment 4, the hypothesis that exposing kindled rats to hippocampal-dependent environmental enrichment would reduce the magnitude of fearfulness, as was shown in Experiment 2. The results supported the hypothesis, particularly for the kindled males. Also in Experiment 4, the survival and dispersal of proliferating hippocampal cells was examined as a function of kindling and enrichment; however, neither manipulation altered cell proliferation. The results of these experiments suggest that behavioural treatments that target the hippocampus are beneficial in reducing the magnitude of kindled fear. The results offer new insights into non-pharmaceutical alternative treatments of anxiety.
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