The effect of left and right long-term amygdala kindling on interictal emotionality and Fos expression

Abstract

Clinical observations have often reported that patients with seizures arising from limbic structures on the right side of the brain have a higher incidence of emotional disturbances, such as fear and anxiety, than those who have seizures lateralized to limbic structures on the left side. However, there have been some inconsistent reports regarding the presence of these laterality effects. The use of animal models of epilepsy can help circumvent many of the methodological and ethical issues that arise from human clinical studies. In the present study, we examined the unique contribution of left- or right-sided long-term kindling of the amygdala on the development of interictal emotional disturbances. Following kindling to 99 electrical stimulations, male kindled and control rats were examined on a series of behavioral tests — open-field exploration, elevated plus maze, forced swim, and social interaction. Our results revealed that long-term amygdala kindling, irrespective of the hemisphere stimulated, increased general behavioral hyperactivity and fearful behavior. Interestingly, rats that were kindled from the left amygdala showed greater social avoidance and defensive behaviors during interactions with another kindled conspecific. To examine the brain structures that support long-term kindling, we also examined the expression of the immediate early gene product Fos 1 h after rats received their last electrical stimulation. Compared with control rats, kindled rats had increased Fos expression in several brain regions (e.g., piriform, frontal motor cortex, perirhinal cortex) involved in the generation and development of epilepsy. However, decreased Fos expression was also observed in several subregions of the hippocampus and amygdala that are known to be important fear behavior and memory. These findings suggest that both left and right amygdala kindling produce similar changes in emotional behavior and support the idea that the development of kindled fear may result from reduced activation of specific hippocampal and amygdaloid circuits.