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Volume 25, Issue 1 (Spring 2023)
Advances in Cognitive Sciences 2023, 25(1): 73-89 |
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Ethics code: IR.IAU.CTB.REC.1401.093
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Poureskandar M, Rahmati S, Entezari Z, Balali M. Investigating the effect of long-term unpredictable mild stress on anxiety, passive avoidance memory, depression-like behavior, and running index of male Wistar rats. Advances in Cognitive Sciences 2023; 25 (1) :73-89
URL: http://icssjournal.ir/article-1-1506-en.html
URL: http://icssjournal.ir/article-1-1506-en.html
1- Department of Motor Behavior, Central Tehran Branch, Islamic Azad University, Tehran, Iran
2- Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran
2- Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran
Abstract: (883 Views)
Introduction
Stress is a set of reactions that occurs in response to any factor that disturbs the internal balance (homeostasis). Stress is known as one of the factors that cause behavioral disorders and may also affect the amount of physical activity, which will be explained more in the following.
Memory is one of the essential variables of the cognitive field that researchers in both animal and human society study. Memory is a mental process that records, stores, and retrieves information; thus, it is exposed to various types of pathological processes, including neurodegenerative diseases, stroke, tumors, head trauma, hypoxia, heart surgery, and malnutrition. Stress can have destructive effects on a person’s learning ability and memory.
Suffering from depression is a combination of genetic and environmental/psychological factors such as insufficient physical activity and stress. Actually, in addition to genetic disorders, some biological factors such as diseases, inactive life, hormonal and neurotransmitter disorders, and some drugs can play a role in the occurrence of depression.
Recently, it has been found that sports activities and exercises have neuroprotective effects and anti-depressant and anxiety effects. Physical activity, specifically aerobic activities performed continuously and continuously, helps reduce nervous and emotional disorders. In addition, aerobic activities prevent and counter the occurrence of many mental disorders and diseases and treat or reduce many of their side effects. As it is known, physical activity has beneficial effects on the body, but stress may cause a decrease in physical activity, and this decrease is probably related to behavioral disorders.
Many studies have investigated the effect of stress on avoidant memory and depressive-like behaviors. Consequently, the results of some of these studies were contradictory. Also, very few studies have investigated the effect of chronic stress on running index. Hence, this study aims to investigate the effect of unpredictable long-term stress on running index, passive avoidance memory, and depressive-like behaviors, as well as investigate the relationship between these variables in male Wistar rats.
Methods
Sixteen male rats were randomly divided into two groups (Each group=8), including experimental and control. The experimental group was exposed to four weeks of stress, while the control group was not under stress conditions. Forty-eight hours after the end of the intervention, behavioral and running index tests were taken from all animals. Rats’ body weight also were measured during the intervention induced. Long-term stress each week consisted of one 18-hour period of food deprivation followed by one hour of food restriction, two periods of 18-hour water deprivation followed by one hour of the empty water bottle, one 21-hour period of being in the wet cage, two periods of 9-hour cage tilt (45°), two 6-hour periods of white noise (85 dB), two 6-hour flashes (150 times per minute), one 24-hour period of light-dark cycles, and one 24-hour period without stressful. The forced swimming test was used to measure the level of hopelessness and despair, as well as the effectiveness of antidepressant interventions. The open box was used to evaluate depression and anxiety in rodents. When an animal is anxious, its natural tendency is to be next to the high walls of the box, and it refuses to go to the center of the environment and search there, and when the anxiety and depression disappear, it walks in all directions to learn more about the world around it. In the present study, the software calculated the total distance the animal moved within 5 minutes. Plus-elevated maze test was used for stress assessment. The elevated maze has two open and closed arms. Rats were individually placed in the center of the elevated maze apparatus facing the open arm and allowed to explore freely for 5 minutes. During this time, the observer (one meter away from the maze) recorded the time the animal remained in the closed arm. The duration of staying in the closed arm indicates the animal's anxiety level. The meaning of entering the closed arm was that all four legs of the animal were placed in the desired arm. A shuttle box device was used to measure passive avoidance memory. The running index was also examined. All data were described as mean and standard deviation. The Shapiro-Wilk test was used to check the normal distribution of the data. According to the normal distribution of the data, parametric statistical methods of one-way analysis of variance (ANOVA) and repeated measures ANOVA were used at a significance level of P<0.05. The effect size was also reported (ηp2). The correlation between the dependent variables of the research was calculated using the Pearson correlation coefficient. Data analysis was done using SPSS version 24 statistical software, and the graphs were drawn using Excel software.
Results
Long-term chronic stress has caused significant weight loss in animals. The time spent in the closed arm (plus elevated maze test) in the long-term stress group was significantly longer than the control group, indicating more anxiety in the experimental group. The duration of immobility (forced swimming test) was significantly longer in the long-term stress group than in the control group, indicating the depression of the rats in the experimental group. The distance covered in the open box test was significantly lower in the long-term stress group than in the control group, indicating the stress and depression of the experimental group. The distance traveled using the spinning wheel was significantly less in the long-term stress group than in the control group. The number of times entering the black box (shuttle box test) in the long-term stress group was significantly higher than in the control group. The duration of staying in the black box in the long-term stress group was significantly longer than the control group. The delay time to enter the black box in the long-term stress group was significantly lower than in the control group, indicating less passive avoidance memory in the experimental group compared to the control group. Stress and depression had a negative and significant relationship with running distance. Furthermore, memory and rats’ body weight correlate positively and significantly with running distance.
Conclusion
In general, the results of the present study showed the destructive effect of long-term stress on memory, anxiety, depression, and running index of rats. According to the correlation results, a better running index is associated with fewer behavioral disorders. One of the limitations of the present study is the lack of measurement of effective physiological factors such as brain-derived neurotrophic factor (BDNF, a key molecule involved in plastic changes related to learning and memory), cortisol, and oxidative stress indicators. The measurement of these physiological indicators can guide us to find a definite mechanism for the effect of stress on the present study variables. Therefore, it is suggested that future studies examine these issues.
Ethical Considerations
Compliance with ethical guidelines
The present study observed all the ethical principles of working with laboratory animals. Besides, the current research has the ethics code number IR.IAU.CTB.REC.1401.093 from Islamic Azad University, Central Tehran Branch.
Authors' contributions
Saleh Rahmati conceived and designed the study. Saleh Rahmati and Maedeh Poureskandar analyzed the data and wrote the manuscript. All the authors contributed to the revision of the paper. All the authors read and approved the final version of the manuscript.
Funding
This article is a part of the PhD dissertation of the first author approved in Islamic Azad University, Central Tehran Branch, Iran. The cost of conducting the research has been provided personally.
Acknowledgments The authors express their gratitude to the staff of Islamic Azad University, Central Tehran Branch, for their cooperation in the research process.
Conflicts of interest
The authors declared no conflict of interest related to this article.
Stress is a set of reactions that occurs in response to any factor that disturbs the internal balance (homeostasis). Stress is known as one of the factors that cause behavioral disorders and may also affect the amount of physical activity, which will be explained more in the following.
Memory is one of the essential variables of the cognitive field that researchers in both animal and human society study. Memory is a mental process that records, stores, and retrieves information; thus, it is exposed to various types of pathological processes, including neurodegenerative diseases, stroke, tumors, head trauma, hypoxia, heart surgery, and malnutrition. Stress can have destructive effects on a person’s learning ability and memory.
Suffering from depression is a combination of genetic and environmental/psychological factors such as insufficient physical activity and stress. Actually, in addition to genetic disorders, some biological factors such as diseases, inactive life, hormonal and neurotransmitter disorders, and some drugs can play a role in the occurrence of depression.
Recently, it has been found that sports activities and exercises have neuroprotective effects and anti-depressant and anxiety effects. Physical activity, specifically aerobic activities performed continuously and continuously, helps reduce nervous and emotional disorders. In addition, aerobic activities prevent and counter the occurrence of many mental disorders and diseases and treat or reduce many of their side effects. As it is known, physical activity has beneficial effects on the body, but stress may cause a decrease in physical activity, and this decrease is probably related to behavioral disorders.
Many studies have investigated the effect of stress on avoidant memory and depressive-like behaviors. Consequently, the results of some of these studies were contradictory. Also, very few studies have investigated the effect of chronic stress on running index. Hence, this study aims to investigate the effect of unpredictable long-term stress on running index, passive avoidance memory, and depressive-like behaviors, as well as investigate the relationship between these variables in male Wistar rats.
Methods
Sixteen male rats were randomly divided into two groups (Each group=8), including experimental and control. The experimental group was exposed to four weeks of stress, while the control group was not under stress conditions. Forty-eight hours after the end of the intervention, behavioral and running index tests were taken from all animals. Rats’ body weight also were measured during the intervention induced. Long-term stress each week consisted of one 18-hour period of food deprivation followed by one hour of food restriction, two periods of 18-hour water deprivation followed by one hour of the empty water bottle, one 21-hour period of being in the wet cage, two periods of 9-hour cage tilt (45°), two 6-hour periods of white noise (85 dB), two 6-hour flashes (150 times per minute), one 24-hour period of light-dark cycles, and one 24-hour period without stressful. The forced swimming test was used to measure the level of hopelessness and despair, as well as the effectiveness of antidepressant interventions. The open box was used to evaluate depression and anxiety in rodents. When an animal is anxious, its natural tendency is to be next to the high walls of the box, and it refuses to go to the center of the environment and search there, and when the anxiety and depression disappear, it walks in all directions to learn more about the world around it. In the present study, the software calculated the total distance the animal moved within 5 minutes. Plus-elevated maze test was used for stress assessment. The elevated maze has two open and closed arms. Rats were individually placed in the center of the elevated maze apparatus facing the open arm and allowed to explore freely for 5 minutes. During this time, the observer (one meter away from the maze) recorded the time the animal remained in the closed arm. The duration of staying in the closed arm indicates the animal's anxiety level. The meaning of entering the closed arm was that all four legs of the animal were placed in the desired arm. A shuttle box device was used to measure passive avoidance memory. The running index was also examined. All data were described as mean and standard deviation. The Shapiro-Wilk test was used to check the normal distribution of the data. According to the normal distribution of the data, parametric statistical methods of one-way analysis of variance (ANOVA) and repeated measures ANOVA were used at a significance level of P<0.05. The effect size was also reported (ηp2). The correlation between the dependent variables of the research was calculated using the Pearson correlation coefficient. Data analysis was done using SPSS version 24 statistical software, and the graphs were drawn using Excel software.
Results
Long-term chronic stress has caused significant weight loss in animals. The time spent in the closed arm (plus elevated maze test) in the long-term stress group was significantly longer than the control group, indicating more anxiety in the experimental group. The duration of immobility (forced swimming test) was significantly longer in the long-term stress group than in the control group, indicating the depression of the rats in the experimental group. The distance covered in the open box test was significantly lower in the long-term stress group than in the control group, indicating the stress and depression of the experimental group. The distance traveled using the spinning wheel was significantly less in the long-term stress group than in the control group. The number of times entering the black box (shuttle box test) in the long-term stress group was significantly higher than in the control group. The duration of staying in the black box in the long-term stress group was significantly longer than the control group. The delay time to enter the black box in the long-term stress group was significantly lower than in the control group, indicating less passive avoidance memory in the experimental group compared to the control group. Stress and depression had a negative and significant relationship with running distance. Furthermore, memory and rats’ body weight correlate positively and significantly with running distance.
Conclusion
In general, the results of the present study showed the destructive effect of long-term stress on memory, anxiety, depression, and running index of rats. According to the correlation results, a better running index is associated with fewer behavioral disorders. One of the limitations of the present study is the lack of measurement of effective physiological factors such as brain-derived neurotrophic factor (BDNF, a key molecule involved in plastic changes related to learning and memory), cortisol, and oxidative stress indicators. The measurement of these physiological indicators can guide us to find a definite mechanism for the effect of stress on the present study variables. Therefore, it is suggested that future studies examine these issues.
Ethical Considerations
Compliance with ethical guidelines
The present study observed all the ethical principles of working with laboratory animals. Besides, the current research has the ethics code number IR.IAU.CTB.REC.1401.093 from Islamic Azad University, Central Tehran Branch.
Authors' contributions
Saleh Rahmati conceived and designed the study. Saleh Rahmati and Maedeh Poureskandar analyzed the data and wrote the manuscript. All the authors contributed to the revision of the paper. All the authors read and approved the final version of the manuscript.
Funding
This article is a part of the PhD dissertation of the first author approved in Islamic Azad University, Central Tehran Branch, Iran. The cost of conducting the research has been provided personally.
Acknowledgments The authors express their gratitude to the staff of Islamic Azad University, Central Tehran Branch, for their cooperation in the research process.
Conflicts of interest
The authors declared no conflict of interest related to this article.
Keywords: Open box test, Forced swimming test, Plus elevated maze test, Passive avoidance memory test, Homeostasis
Type of Study: Research |
Received: 2022/12/28 | Accepted: 2023/05/9 | Published: 2023/07/10
Received: 2022/12/28 | Accepted: 2023/05/9 | Published: 2023/07/10
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