
2023 Impact Factor
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.
Depression is a serious disorder characterized by either a depressed mood or anhedonia, weight changes, sleep disturbances, psychomotor agitation, fatigue, feelings of worthlessness, diminished cognitive functioning, or recurrent thoughts of death. Stressful experiences have been reported to favor the development of depression in humans (Kessler, 1997; Kendler
There has been an increasing number of studies on CMS effects in mice although most studies were previously performed in rats. It has been reported that the CMS paradigm in mice elicits a decrease in responsiveness to rewards, as revealed by decreased palatable sucrose consumption (Pothion
Previous studies showed that there are differences between strains of mice in the sucrose consumption test (Pothion
Generally, high comorbidity rates of depression and anxiety are observed in depressed patients, and the margins between depression and anxiety become blurred, which suggests that these disorders may not be entirely distinct conditions in humans or animals (Kaufman and Charney, 2000). Increases in anxiety-related behavior and locomotor disturbances were found to be induced by the stress procedure (Strekalova
In the present study, we examined the impact of differences in responsiveness to CMS on “anhedonia” (sucrose consumption) and depression- and anxiety-like behaviors in different strains of mice. We investigated the effects of CMS on different tests measuring anxiety- and depression-like behaviors using the sucrose intake test, forced swimming test, open field test, and novelty-suppressed feeding test. C57BL/6 and ICR strains of mice were selected because they are representative of inbred and outbred strains, respectively. Also, they are the most widely used strains in various behavioral tests. The purpose of this study was to identify potential behavioral differences in depression and anxiety between C57BL/6 and ICR strains after CMS treatment.
Male C57BL/6 (J) and ICR mice weighing 22?30 g were purchased from Dae Han Biolink, Co., Ltd (Eumseong, Korea). The animals were housed 4?5 mice per cage in a temperature-and humidity-controlled room (23 ± 1°C, 55 ± 5%) under a 12-h light/dark cycle (light on 07:00?19:00) and allowed access to food and water ad libitum. After arrival, mice were acclimatized for 1 week prior to use in experimental procedures. Mice were introduced to the experiment room at least 1 h before the behavioral tests. All animal care procedures were conducted in accordance with the U.S. National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of Sungkyunkwan University.
The CMS procedure was performed as described (Elizalde
The SIT was conducted as described (Gronli
Locomotor activity was assessed by OFT after 3 weeks of CMS exposure. The open field consisted of an opaque plastic box (30×30×30 cm) divided into 16 (4×4) identical sectors (7.5×7.5 cm). The field was subdivided into peripheral and central sectors, where the central sector included 4 central squares (2×2) and the peripheral sector was the remaining squares (Li
The FST was carried out on mice according to the method of Porsolt (Porsolt
The NSF test was performed according to a modified procedure, as described previously (Jang
Data are expressed as the means ± SEMs. The data were analyzed by two-way ANOVA followed by the Bonferroni post hoc test using Prism 5.0 (GraphPad Software, Inc., USA). Significant differences were set at the
Before the onset of CMS, sucrose intake was similar in both the control group and in the group of mice that were to undergo stress. In ICR mice, there was a significant interaction between stress and time (F1,80=3.897,
After 3 weeks of CMS exposure, the open field test was performed to evaluate locomotion and anxiety-like behaviors. The stressed mice showed increased movement without significant changes compared to the control mice in both strains (Fig. 3A). In addition, the two strains of ICR and C57BL/6 mice caused significant central activities in the open field test. Both strains, ICR and C57BL/6 mice, showed significant decreases in time spent in the center after CMS (ICR: t=2.438,
Depression-like behavior of the different strains in the FST is shown in Fig. 4. The stressed C57BL/6 mice significantly showed depressive behavior by displaying increased immobility compared to the non-stressed mice after CMS (t=2.548,
The NSF test measures food consumption in a novel environment under food deprivation, where reduction is interpreted as anxiety-like behavior as well as depression-related behavior (Bodnoff
In the present study, we assessed potential differences between one outbred (ICR) and one inbred (C57BL/6) mouse strain in response to different types of behavioral tests in the CMS model. The present data showed marked differences between the two mouse strains in their responsiveness to the CMS procedure. The C57BL/6 mice showed depression- and anxiety-like behavioral effects in the SIT, OFT, FST, and NSF tests after 3 weeks of CMS treatment. However, ICR mice failed to display depression-like behaviors in the FST and NSF tests.
CMS is generally thought to be the most promising and valuable rodent model for studying depression in animals because it mimics several human depressive symptoms. Moreover, genetic factors, such as strain differences, may contribute to the behavioral performance of mice in models of depression. Previous studies reported that there were differences between strains of mice in sucrose intake (Pothion
Reduced consumption of sucrose solutions induced by CMS has been used as a measure of anhedonia, a major symptom of depression (Willner
When testing anxiety-related behaviors in the open field, similar effects on CMS were obtained in both strains. When the mice were placed in a novel environment, increased tendencies of locomotor activity in the stressed mice were observed. A previous study reported that CMS-treated mice showed more activity than control mice in the open field (Mineur
Some strain differences have been described previously for the tail suspension test (Liu
The NSF test is often used as an additional measurement of depressive behavior and is also used to assess chronic antidepressant efficacy in rodents (Santarelli
In this study, we found that the C57BL/6 and ICR strains of mice displayed different responsiveness to CMS through depression- and anxiety-like behaviors. It should be mentioned that there might be relevant neurochemical differences between two strains that could influence behavioral responsiveness. Previously, it has been reported that a specific and regionally differentiated serotonin-dopamine interaction is directly related to the observed stress-induced anhedonia in different rat strains (Bekris
In summary, this study showed that different strains of mice exhibited different behavioral patterns in various animal models including the SIT, OFT, FST, and NSF tests. The inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in SIT and OFT. However, two strains showed quite different responses in FST and NSF test. Only C57BL/6 mice displayed depression- and anxiety-like behavioral effects to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression-and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.