Background: High salt intake increases the active coping behavior during psychological stress. Acute fear-related severe stress enhances passive coping behavior during subsequent inescapable stress. Methods: We investigated the effect of high salt intake (2%) for 5 consecutive days on the coping behavior in C57BL6 mice which employing the tail suspension test (TST) at 1 h after the exposure to inescapable innate fear using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic component of fox feces. By using a different mouse group, to investigated whether anxiety-like behavior was correlated with coping behavior during the TST, we performed the elevated-plus maze (EPM) test at 1 h before the TST without TMT. Results: Both the distance traveled and the number of entries in the central zone of test box during TMT were negatively correlated with freezing time in both sodium-and water-intake mice. Sodium-intake increased the preference for central zone during TMT exposure, but did not change fear sensitivity and locomotor activity. Sodium-intake also prevented that TMT-induced increase in the immobility time during TST. The immobility time during TST was positively correlated with freezing time during TMT exposure in sodium-intake, but not in water-intake mice. Furthermore, the immobility time during TST in sodium-intake mice correlated with the distance traveled and with the number of entries in the central zone during TMT. Sodium intake also increased the number of entries and the time spent in the open arm of the EPM, indicating that high salt intake had an anxiolytic effect. However, neither the number of entries nor the time spent in the open arm of the EPM were correlated with immobility time during TST in sodium-intake mice. Conclusions: We conclude that a high salt intake induces active coping behavior after experiencing fear stress by enhancing stress resilience rather than by reducing the anxiety level.

The synaptic plasticity in the bed nucleus of stria terminalis (BNST) is induced by the activation of α 1 and βadrenergic receptors, and/or NMDA receptors. We previously reported the possibility that the synaptic plasticity in BNST contributes to the induction of depressive-like behavior, because the α 1 and β-receptors in BNST regulated the learned despairs in mice. However, neither α 1 nor β-receptors in BNST affected the lipopolysaccharide (LPS)induced behavioral despair in mice. Therefore, we investigated whether the NMDA receptors in BNST contribute to the induction of LPS-induced behavioral despair. The bilateral intra-BNST pretreatment of MK-801, a NMDA receptor antagonist, 30 min prior to LPS injection, decreased the immobility time during tail suspension test (TST) 24 hours after the LPS challenging. In consistent, bilateral intra-BNST injection of NMDA (24 mg/125 nl/side) slightly shortened the immobility time during TST. However, bilateral intra-BNST co-injection of muscimol (75 ng/125 nl/side), a GABA A receptor agonist, with NMDA potently decreased the immobility time during TST. Because this dose of muscimol alone did not affect the immobility time of TST, in the present study, we suggest that the activation of NMDA receptors with GABA A receptors in BNST is important for the induction of depressive-like behavior.

A component of fox faces, 2,4,5-trimethylthiazoline (TMT) induced innate fear of mice produced active escape behaviors in inescapable box is followed by freezing as passive escape behavior. The duration of active escape behavior is regulated by the neurons releasing the corticotropin-releasing hormone from the paraventricular nucleus of hypothalamus to the bed nucleus of the stria terminalis. Recently we found that the 2% salt intake for 5 days decreased the duration of TMT-induced active escape behaviors and increased the duration of freezing time in inescapable acryl box (30 cm 3). Against our expectation, the mice with 2% salt intake exhibiting shorter duration of active escape behaviors delayed the induction of learned despair during tail suspension test (TST) and decrease in the duration of the immobility time during TST, because the paradigm of innate fear-induced inescapable behaviors from active to passive coping strategies is similar with that of TST. Excessive daily salt intake is the risk for the high blood pressure, myocardial infarction and stomach cancer etc. In the present study, we suggest that the tasting the adequate amount of salt, but not excessive, may decide the coping style to adapt the psychological stresses and benefit for preventing the despair behavior as enhancing the resilience against daily stresses.

Re-experiencing trauma by overgeneralization is a hallmark of PTSD which is high comorbidity with depression. We thus studied the relation from overgeneralization to depression. Mice were subjected to context A with electric shock as a conditioning which was followed by unconditioned context B using a different, but similar box in 3h on Day1 and was followed by re-exposure to context A (Group ABA) or B (Group ABB) on Day2. Group ABA and ABB mice exhibited the longer freezing in context A and B on Day2. However, the mice which was not exposed to context B on Day1 (Group A-B) showed the shorter freezing time in context B on Day2, indicating that the overgeneralization was induced by experiencing the context B after the conditioning in 3 h. Group ABB mice exhibited the longer immobility time of tail suspension test (TST) than Group ABA and A-B. Freezing time in the first half of the test in context B and immobility time of TST in Group ABB were negatively correlated with the staying time of center zone in the box during the context B on Day1. In contrast, the freezing and immobility time of TST in Group ABA have positive correlation with the time of center zone during context B on Day1. These results suggest that the PTSD and depression may depend on the coping style during unconditioned context within a few hours after the trauma.