3% ± 8.2%, n = 9; DR in stressed: −11.0% ± 8.3%, n = 9, p < 0.001). To test the specificity of this stress-induced memory deficit, we also subjected animals to the object location task, a paradigm for the PFC-independent memory (Barker et al., 2007). As shown in Figure 1D, both control groups and stressed animals (restraint, 7 day) showed similar discrimination between the object that had changed position than the object that had remained in a constant position (DR in control: 58.1% ± 5.4%, n = 6; DR in stressed: 47.7% ± 15.7%, n = 6, p > 0.05). In contrast to the impaired temporal order recognition memory, rats exposed to
repeated restraint stress showed no changes in anxiety-related behavior or selleck inhibitor locomotive activity (Figure 1E), as indicated by the amount of time spent in the open-field center (control: 7.3 s ± 0.9 s; stressed: 7.3 s ± 1.5 s, n = 8 pairs, p > 0.05) and the number of midline crossing in a cage (control: 10.2 ± 1.2, stressed: 11.5 ± 1.8, n = 6 pairs, p > 0.05). To find out the onset of the detrimental effects of stress on cognition, we exposed young male rats to various days (1,
3, 5 and 7) of restraint stress. PI3K Inhibitor Library cell line As shown in Figure 1F, TOR memory was largely unchanged by 1 or 3 day stress but was significantly impaired in animals exposed to 5 or 7 day stress (p < 0.001, n = 6 pairs per group). After 3 day withdrawal from the repeated stress, TOR memory still showed deficiency (p < 0.01, n = 6 pairs) but recovered after 5 day withdrawal (n = 6 pairs). To test whether glutamatergic transmission in PFC is critical for the object recognition memory, we gave animals a stereotaxic injection of the NMDAR antagonist APV and AMPAR antagonist CNQX to PFC prelimbic regions bilaterally. As shown in Figure 1G, APV+CNQX-injected animals lost the normal preference to the novel (less
recent) object (DR in saline: 36.8% ± 10.3%, n = 7; DR in APV+CNQX: −20.4% ± 8.7%, n = 11, p < 0.001), similar to the animals exposed to repeated stress. The total exploration time in the two sample phases and the subsequent test trial was unchanged by any of these treatments (Figure S1 available online). Taken together, it Cytidine deaminase suggests that repeated stress has a detrimental effect on recognition memory, which may be due to the loss of glutamatergic transmission in PFC. To find out the impact of repeated stress on glutamatergic transmission, we examined the input/output curves of AMPAR- and NMDAR-mediated synaptic currents (EPSC) in PFC pyramidal neurons from stressed, young (4-week-old) male rats. As shown in Figures 2A and 2B, AMPAR-EPSC and NMDAR-EPSC induced by a series of stimulus intensities were markedly reduced in neurons from animals exposed to repeated (7 day) restraint stress or unpredictable stress (AMPA: 40%–60% decrease, p < 0.01, ANOVA, n = 16–29 per group; NMDA: 38%–57% decrease, p < 0.