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

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.

Heat shock proteins 27 and 70 regulating angiotensin II-induced NF-kappaB: a possible connection to blood pressure control?

Heat shock proteins (HSPs) are critical for cell survival and have several mechanisms of action. HSPs regulate protein folding, suppress apoptosis, and regulate anti-oxidative activity. In addition, HSPs are involved in the regulation of the pro-inflammatory transcription factor nuclear factor (NF)-kappaB. When angiotensin (Ang) II is infused into rats, there is a significant increase in systolic blood pressure, and NF-kappaB is activated in the heart. If rats are heat shocked to induce the heat shock response and HSPs before Ang II infusion, there is a significant suppression of both the Ang II-induced increase in blood pressure and NF-kappaB activation in the heart. Although the role of specific HSPs in the regulation of NF-kappaB is unclear, several HSPs, including Hsp27 and Hsp70, are thought to be involved in the regulation of Ang II-induced NF-kappaB. The role of Hsp27 and Hsp70 in NF-kappaB activation is reviewed here, along with evidence suggesting that HSPs regulate Ang II-induced blood pressure through the regulation of NF-kappaB.

Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats.

Repeated stress is an important risk factor for the development of depression. However, the mechanism by which stress influences depression is largely unknown, in part due to the fact that few animal models of repeated stress produce robust changes in depression-like behavior. The purpose of the present study was to characterize the effect of repeated corticosterone (CORT) injections and repeated restraint stress on anxiety and depression-like behavior in male rats. Rats received CORT injections (40 mg/kg, s.c.), vehicle injections, restraint stress (6 h/day), or handling once per day for 21 consecutive days prior to the behavioral testing. The rats were then tested for changes in fearful/anxious behavior in the open-field and social interaction tests and for depression-like behavior in the forced swim test. The repeated CORT injections had no significant effect on activity levels or anxiety in the open-field or social interaction tests. However, they did increase depression-like behaviors in the forced swim test. Repeated restraint stress had no significant effect on anxiety or depression-like behavior on any of the behavioral tests. These results suggest that repeated CORT injections warrant further investigation as an animal model to study the role of stress in depression.

Environmental enrichment facilitates amygdala kindling but reduces kindling-induced fear in male rats.

The purpose of this experiment was to determine the effect of prior environmental enrichment on the acquisition of kindling and the expression of kindling-induced fear. Sixty male rats were housed either in an enriched environment or in isolation, starting immediately after weaning. As adults, they were subjected to either 50 amygdala-kindling stimulations or sham stimulations, followed by testing in an unfamiliar open field. The kindled-enriched rats acquired the kindled state more quickly than did the kindled-isolated rats, but they also showed less fear in the open field than did the kindled-isolated rats. These results suggest that environmental enrichment has differential effects on kindling acquisition and its behavioral consequences.

Kindling-induced emotional behavior in male and female rats.

Modeling fear in animals is a critical approach for identifying the neural mechanisms involved in human disorders such as generalized anxiety and panic. Amygdala kindling has proven useful in this regard because it produces dramatic increases in fearful behavior. The purpose of this experiment was to compare the behavioral effects of kindling in male and female rats. Compared with the sham-stimulated rats, the kindled male and female rats showed similar increases in fearful behavior, with some sex differences in fear-related open-field activity. They also showed decreased immobility in the forced-swim test and increased sucrose consumption. These results suggest that kindling-induced fear is generally similar in male and female rats and that kindling does not appear to induce depression-like behavior.