Stress on learning and memory
Based on the results, immobilitystress significantly destroyed learning, which was confirmed by an increase in the distance to the platform in the stress group. Brain structure underwent some changes due to the high accumulation of glucocorticoid receptors in the hippocampus. Stress-induced adrenal hormones can affect the structure of the hippocampus [23]. Long-term exposure to stress or glucocorticoids causes many alterations in the structure of the hippocampus such as neurochemical changes, irritability, neurogenesis, neuronal morphology, and even cell death [24]. However, the effects of pre-learning stress are inconclusive since many studies have reported its reinforcing effect [25] while others have shown its destructive effect on spatial memory and hippocampal-related events [26]. A recent study suggested that stress disrupts memory, control circuitry, route neural replay, and behavior and provides mechanistic insights into why and how stress can alter planning and foster inefficient behavior [3]. Stress is not necessarily good or bad for cognitive processes such as memory recovery. Different mechanisms and mediators play significant roles in responding to stressors. Several studies examining the effects of stress on spatial learning in MWM reported that chronic stress has multiple effects, which may be related to the type of stressors, length of the period, and severity of the stress. For example, the results of the previous research indicated that chronic stress resulting from five months of unstable maintenance conditions [27], one month of unexpected stress [28], and limited mobility for seven days [29] or 21 days [26] can disrupt learning. In contrast, chronic stress caused by continuous light for 21 days [25], unexpected stress for 10 days [13], or recovery after a month of unexpected stress [28] can facilitate learning. In addition, chronic motor stress (six hours a day for 21 days) produced no effect [26]. The possible interpretation of the different results is that the type of stressor, length of the period, and intensity of stress are considered as effectivefactors. For example, continuous light exposure for 21 days or movement restriction for 10 days may be less severe than 21 days of movement restriction or 5 months of storage in unstable conditions. On the other hand, animal breeds can be effective in responding to stress. In the previous study, two hours of inactive stress per day for 3 weeks disrupted learning among Wistar rats [29], which is inconsistent with the results of other studies using other breeds [30,31].Thus, the breed type may be responsible for some differences. To measure spatial memory in the Morris water maze, the effects of chronic stress are ambiguous. Our results are inconsistent with some other studies observing memory impairment [29] and those reporting ineffectiveness [26]. These contradictory results can be attributed to many variables such as the nature, duration of the stressors, nature of the task, and characteristics of the subject (e.g., age and sex) [32].
Physical exercise on learning and memory
In this study, four weeks of aerobic exercise with a treadmill failed to produce a significant effect on learning and memory. Unexpectedly, the swimming practice slowed down the learning process based on the average distance traveled to reach the platform. Additionally, no significant difference was observed in this group in the duration and speed of reaching the platform as well as the probe tests compared to the control group.
Several studies reported that voluntary and compulsive exercise improved synaptic formability in the hippocampus [33] and spatial learning [9]. This discrepancy may be related to the differences in the length and severity of the exercise protocol. On the other hand, some studies noted that the type of learning test can be effective in obtaining different results [34]. In the study, after 2-3 months of optional exercise, a significant improvement was observed in spatial learning [35] while other studies reported performance improvements in radial arm maze after 7 weeks of optional exercise [36]. Additionally, some other studies showed performance improvements in Morris water maze in the youth ranks after a week of optional exercise [37]. However, due to the inherent stress involved in compulsory exercise, it is assumed that this type of exercise may not induce beneficial effects during the acquisition phase. However, this hypothesis is somewhat challenging, as reports suggest that gentle treadmill training can improve spatial learning in the elderly [38]. In a review article, the analysis of 107 studies examining the role of aerobic exercise on the nervous system indicated that the rehabilitation role of aerobic exercise protocols is very important in improving learning efficiency. Furthermore, these protocols are important in the possible treatment of the memory-related disorders in the central nervous system [7]. A recent review demonstrated that chronic stress associated with memory impairment and chronic exercise within animal models has both a preventive and therapeutic effect on attenuating stress-induced memory impairment [8]. The findings are consistent with some other studies indicating exercise had no effect on memory [9,39]. Differences in test types to evaluate the effects of exercise on memory can cause differences in the obtained results [34]. Further, different exercise protocols with various intensities could exert different effects on neural functions [8].
Citalopram on learning and memory
Based on the results of the present study, citalopram did not improve stress-related damage in the learning process, but slowed down the learning process. However, despite the increase in the average time and distance traveled to the platform, this increase is not significant compared to the stress group. In addition, a significant difference was observed between the two groups in the distance and time required to reach the platform on the second day, which indicates a decrease in the learning process of the consumer group of citalopram in comparison to the stress group.
Previous research on the effects of anti-stress and anti-depressant drugs on memory and learning provided inconclusive results. Some studies supported the theory that SSRIs and citalopram lead to disruption in various forms of learning after injection or acute use [11,40]. Acute treatment with fluoxetine did not impair inhibitory learning while chronic treatment led to memory impairment in the inhibitory learning test among rats [41]. Citalopram resulted in memory impairment at 10 and 20 mg / kg in the active avoidance test among rats while it had no effect on memory in the inhibitory avoidance test (one and three mg/kg) [42]. However, Zhang et al. found that the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without any alterations in the hippocampus, which might contribute to the improvement of behavioral performance. The findings suggested that citalopram can be considered as a potential candidate for the early treatment of AD [12]. In some studies, low doses of citalopram were useful in treating memory deficits and impaired consciousness [20]. It seems that the differences in previous studies can be related to the differences in drug doses, administration route, sex and species of the animals, different test protocols, and the existing conditions. However, in this study, in comparison with stress groups, citalopram consumption did not improve the learning process, counteracted the negative effects of stress, and increased the distance and time spent on the platform. Thus, there was a significant difference between this group, the swimming + stress group, and the treadmill + stress group in terms of the distance traveled to the platform. Furthermore, considering memory impairment as a side effect of SSRIs, more attention should be paid to the pharmacological treatment of various mood disorders such as depression, stress and Alzheimer’s, especially in old age, and mental decline conditions.
Physical exercise after stress on learning and memory
The results indicated that in the group of aerobic exercise with a treadmill under stressful conditions, despite the decrease in the average distance and time spent to find the platform compared to the stress group in the acquisition stage, no significant difference was observed between two groups in the mean time and distance. In addition, in the probe test, no significant difference was observed although there was an increase in the amount of time spent in the quarter of the target. Contrarily, in the swimming training group under stress conditions, there was a considerable improvement in the learning process and a significant difference between this group and the stress group in terms of mean distance to reach the platform. However, despite the increase in the amount of time spent in the quarter of the target, no significant difference was observed in the probe test.
Unlike the findings of this study, Kim et al. (2011) failed to observe a significant difference between stress groups and stress-exercise [43]. It is noteworthy that the exercise protocol in Kim et al. was longer than that of the present study in terms of duration (8 weeks of running on a treadmill) and intensity. In this case, the previous research showed that the activity of the HPA axis gradually increased as the training period increased from 9 to 24 days [44]. Therefore, the increase in corticosterone levels could be attributed to the length of the training period. However, it seems that the normal functioning of learning and spatial memory, which was impaired by stress, may rely on physical activity. In addition, corticosteroids can be used as a mediator in the protective role of exercise against the destructive effects of stress. Other possible mechanisms include increased exercise-induced neurogenesis, increased expression of neurotransmitters such as BDNF and NGF [45], and long-term enhancement (LTP) [35]. In the latter case, it is generally believed that LTP may be the basis of some memory underlying events [46] such as the formation of dendritic appendages.