Post-consolidation treadmill exercise modulates the expression of defensive responses to persistent fear memories in female, but not in male rats.

While physical exercise (PE) acts as a modulator of memory acquisition, its influence on the persistence of consolidated fear memories remains paradoxical in the literature. This divergence suggests that PE can either strengthen or attenuate the original mnemonic trace, as this effect may be conditioned by the initial learning intensity and biological variables, such as sex. This study investigated how a 14-day treadmill PE protocol, initiated after memory consolidation, influences the persistence of contextual fear conditioning (CFC) memory acquired under different learning intensities (0.3 mA or 0.7 mA) in male and female Wistar rats. Memory was assessed at 24 h post-acquisition and then at 15 and 30 days after the start of the PE, using the percentage of freezing (passive defense strategy) and escape behavior (active defense strategy). Results demonstrated that PE had a sex-specific and intensity-dependent modulatory effect. In females, PE significantly reduced the freezing behavior in the 15-day test, specifically in the group that acquired high-intensity memory (0.7 mA). However, this reduction in freezing was accompanied by a significant increase in escape responses, indicating a shift in the defensive strategy. Conversely, PE did not modulate freezing or escape behavior in males at either intensity. Our findings suggest that 14 consecutive days of PE have the potential to attenuate the freezing but not escape behavior, specifically in females. These results reinforce the necessity of considering sex as a biological variable in this type of study and highlight the importance of including the analysis of active behavioral strategies, despite the more traditional one (freezing) in fear memory research.