Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic–pituitary–adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. The difference in freezing levels between B-3h and B-24h in Hy-Crf-KD mice was larger than that of controls. In Hy-CRF-OE mice, the freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. Locomotor activity before CS and freezing level during CS were similar among the groups. Therefore, we hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.

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.

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.