Altered synapsin I immunoreactivity and fear behavior in male and female rats subjected to long-term amygdala kindling

Abstract

Long-term amygdala kindling dramatically increases fearful behavior in both male and female rats. In this experiment, we studied the relation between sex, kindled fear behavior, and synapsin I immunoreactivity in various brain regions. Male and female adult Long-Evans rats received either 99 left amygdala kindling stimulations or sham stimulations. One day after the final stimulation, fear behavior was assessed in each rat by measuring exploration and thigmotaxia in an unfamiliar open field, as well as resistance to capture from the open field. Four hours after the behavioral testing, the rats were sacrificed and their brains were processed for immunohistochemical determination of synapsin I expression. As expected, kindling significantly increased fear behavior in both male and female rats. It also increased synapsin I immunoreactivity bilaterally in most hippocampal subfields, but not in the caudate nucleus, sensorimotor cortices, or piriform cortex. Interestingly, kindling decreased synapsin I immunoreactivity bilaterally in the central and basolateral amygdala of male rats but not female rats. Correlational analyses revealed that in male rats, fearful behavior was positively correlated with synapsin I immunoreactivity in hippocampal brain regions located ipsilateral to the site of stimulation (i.e., the CA1 and CA3 subfields of the hippocampus, the dentate gyrus and the hilus) and negatively correlated with synapsin I immunoreactivity bilaterally in the basolateral and central amygdala. In female rats, fear behavior was positively correlated with synapsin I immunoreactivity in the ipsilateral CA1 and CA3 subfields only. These results suggest that altered synaptic plasticity in specific brain regions might be involved in the exaggerated fearfulness produced by long-term amygdala kindling, especially in male rats.