Acute Stress Alters Recognition Memory and AMPA/NMDA Receptor Subunits in a Sex-dependent Manner

Several studies have consistently reported a detrimental effect of chronic stress on recognition memory. However, the effects of acute stress on this cognitive ability have been poorly investigated. Moreover, despite well-documented sex differences in recognition memory observed in clinical studies, most of the preclinical studies in this field of research have been carried out by using solely male rodents. Here we tested the hypothesis that acute stress could affect the consolidation of different types of recognition memory in a sex-dependent manner. For this purpose, male and female C57BL6/J mice were exposed to 2-h of restrain stress immediately after the training session of both the novel object recognition (NOR) test and novel object location (NOL) tasks. Acute restraint stress did not affect memory performance of male and female mice, after a 4-h delay between the training session and the test phase of both tasks. By contrast, acute restraint stress altered memory performance in a sex-dependent manner, after a 24-h delay. While stressed mice of both sexes were impaired in the NOL test, only male stressed mice were impaired in the NOR test. Because ionotropic glutamate receptors-mediated neurotransmission is essential for shaping recognition memory, we further tested the hypothesis that post training acute stress could induce sex-dependent transcriptional changes of ionotropic glutamate receptor subunits in the dorsal hippocampus. We uncovered that acute stress induced sex-, time- and type of memory-dependent transcriptional changes of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. These findings suggest that the effect of acute stress on recognition memory can be strongly biased by multiple factors including sex. These findings also indicate that the same stress-induced memory impairment observed in both sexes can be triggered by different sex-dependent molecular mechanisms. At the therapeutic level, this should not be overlooked in the context of personalized and targeted treatments.