This study was conducted to compare the depression-inducing effects of immobilization stress and chronic mild stress in female rats. We observed that both stress models caused a significant increase in immobility duration and a decrease in swimming duration. In the forced swimming test, immobility scores are used as an index of behavioral despair
22. Therefore, rendering behavioral despair in this test is one of the main approaches to depression-related behavior in experimental studies
23 because this behavior may be modulated by a wide range of antidepressants
22,24. In a 10-day chronic stress study, the researchers used two different chronic stress models: restraint in small cages and immobilization in adaptable plastic cones, and they reported that two stress paradigms induced depressive-like behaviors in rats
25. In our previous experiments, we determined that both 45-minute daily immobilization stress for 10 days and 21 days of chronic mild stress induce depression-related behaviors in female rats
13,15. However, we obtained different results in our previous study in male rats
18. We used two immobilization models, immobilization-1 (45 minutes daily for a period of ten days), and immobilization-2 (45 minutes twice a day for a period of ten days), both of which caused a significant increase in anxiety-like behaviors in adult male rats. These different results can be interpreted as a result of gender-related effects in such diseases
3,4.
Comorbidity between depression and anxiety is an essential issue in humans 26. The same condition may be true for small rodents. Indeed, in our previous study, we determined that long-term social isolation stress induces both depression- and anxiety-related behaviors in rats 21. Moreover, we observed that anxiety-like behaviors predominated than depression-like behaviors in the immobilization stress-treated adult male rats 18. Therefore, we also evaluated the possible anxiety-related behavior-inducing potentials of 10 days of the chronic mild stress and 10 days of 45-minute per day immobilization stress models. In the open field test, we determined that the percentage of time spent in the central area was lower in the chronic mild stress and immobilization stress models, but it reached a statistically significant value only in the immobilization stress group. The values of latency in the central area and rearing frequency were lower in the immobilization stress group. However, there was no significant alteration in the chronic mild stress and immobilization stress groups for the scores of total distance, mean velocity and grooming behavior. These results mean that an immobilization stress procedure can cause a partial comorbidity between depression and anxiety, but chronic mild stress induces depression-related behaviors in female rats. In a 21-day chronic immobilization stress study, researchers reported that immobilization stress caused depression in Sprague Dawley male rats 27. In mice, there are several studies that reported that 120 minutes of chronic immobilization stress per day for 10 days causes increased anxiety-related behaviors 28,29. These different results indicate that the intensity and duration of applied stress as well as species and gender are important in modeling these disorders 30,31.
We also evaluated the percentage of body weight change in two models after 10 days of stress. There was a significant difference in the percentage of body weight change in the chronic mild stress group. This result is an important clue for evaluating the effects of both stress models on the body weights of rats. A significant weight loss is in a symptom profile of chronic mild stress 32. The same result may also be true for immobilization stress 33. However, it is useful to state that these effects are related to the length of the stress period. Especially in long-term chronic mild stress protocols, when food and water restriction are included among the stressors, weight loss can be observed in the animals due to these factors. Therefore, it is suggested that chronic mild stress models which do not include food and water restriction would be more useful models 34. Since we applied a chronic mild stress model for 10 days, we think that stress procedure, rather than stress period itself, might have had an effect on the weight loss in the animals. Food deprivation, 60-degree cage tilting and wet cage procedures have a high potential to adversely affect the feeding routine of the animals. These stress factors were important causes of weight loss in the chronic mild stress group. Importantly, this stress protocol may be associated with some disadvantages in modelling pregnancy or postpartum depression. In relation to weight loss in animals, abortion may occur in pregnant animals, or death of pups may result among lactating animals due to insufficient milk yield.
In conclusion, we suggest that the depression-related behavior-inducing potential of the chronic mild stress model is more prominent than the immobilization stress model (45 minutes per day) by means of 10-day stress protocol in female rats. However, our chronic mild stress protocol might have some risks in animals during the pregnancy and postpartum period due to significant weight loss.