• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.321-329
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• 2013

Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST.

• 동의신경정신과학회지
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• 제24권3호
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• pp.281-292
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• 2013

Objectives : A growing body of evidence has suggested that the dysfunction of glutamatergic systems plays a pivotal role in major depressive disorder (MDD). This study was performed to investigate the antidepressant-like effects of the ethanolic extract of Gastrodia elata Bl (GE) in mouse models and to investigate the role of ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in producing these antidepressant-like effects. Methods : The forced swim test (FST) and tail suspension test (TST) were used to investigate GE's behavioral effects in mice. Additional biochemical and behavioral experiments with NBQX, an AMPA receptor antagonist, were undertaken to determine whether the antidepressant-like properties of GE are involved in AMPA receptor throughput. Results : Oral administration of GE extract (1,600 mg/kg) 1h prior to testing significantly reduced the immobility times in the FST and TST. These antidepressant-like effects of GE extract were increased dose-dependently. Pre-treatment with NBQX significantly attenuated the reduction in immobility time induced by the GE extract in the FST and TST. Conclusions : The ethanolic extract of GE may exert antidepressant-like effects with involvement of AMPA receptor.

• Biomolecules & Therapeutics
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• 제27권4호
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• pp.349-356
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• 2019

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the "antidepressant" properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

• 동의신경정신과학회지
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• 제24권3호
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• pp.271-280
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• 2013

Objectives : The development of natural drugs with antidepressant effects is important and needed. This study was performed to investigate the antidepressant-like effects of the distilled water extract of Portulaca oleracea L. (POL) in a mouse model and to investigate the role of ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in producing these antidepressant-like effects. Methods : The forced swim test (FST) and tail suspension test (TST) were used to investigate the behavioral anti-depressive-like effects of POL in mice. Additional behavioral experiments with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, an AMPA receptor antagonist, were undertaken to determine the involvement of the antidepressant-like properties of POL in AMPA receptor throughput. Results : Oral administration of the POL extract (100 mg/kg) 1 h prior to testing significantly reduced the immobility times in the FST and TST. The antidepressant-like effects of the POL extract were not increased in a dose-dependent manner. Pre-treatment with NBQX significantly attenuated the reduction in immobility time induced by the POL extract in the FST. Conclusions : The distilled water extract of POL has antidepressant-like effects, which may be related to AMPA receptor. Pre-treatment with NBQX significantly attenuates the reduction in immobility time induced by the POL extract in the FST.

• Toxicological Research
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• 제19권2호
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• pp.99-104
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• 2003

This study was aimed to evaluate the effect of oxygen on motor activity and toxicity in male mice. The modified Porsolt forced swim test (FST) was used and the distance and time of movement by mice were analyzed in 15。C water bath for 20 minutes using the automatic Ethovision videotracking system. Analyses were carried out before and after 20 minutes of exposure to 10％-70％ concentration of normobaric oxygen. The effects of inspired oxygen tension on the distance and time of movement showed the similar trends, but changes in distance were more prominent. Both the distance and time of movement increased after exposure to 30％ and 40％ oxygen concentration. The distance and time of movement also increased upon exposure to 50％ and 60％ oxygen. In contrast, increases En movement and time under exposure to 21％ oxygen concentration were suppressed when exposed to over 50％ oxygen concentration. With exposure to 10％ oxygen, there was a significant decrease in the distance of movement and a slight suppression of movement time. During the swim test, 12.5％, 37.5％, and 87.5％ of the mice drowned after exposure to 10％, 60％, and 70％ oxygen concentration, respectively. These results suggest that motor activity can be enhanced by inspired oxygen up to 40％ concentration. When hypoxic and hyperoxic oxygen exposure over 50％, motor activity is reduced and toxicity may be induced.

• 생물정신의학
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• 제27권1호
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• pp.27-35
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• 2020

Objectives Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. Methods In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively. Results In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012). Conclusions We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

• 정신신체의학
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• 제8권1호
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• pp.46-57
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• 2000

연구목적 : 본 연구는 선택적 세로토닌 재흡수 차단제인 paroxetine과 sertraline의 마우스에 대한 아급성 처치가 강제수영시험에서의 부동자세 시간과 강제수영시험으로 유발된 면역능의 변화에 미치는 영향을 조사하고자 시행되었다. 방법 : 저자들은 실험동물로 각 군마다 5마리 이상의 BALB/c 마우스를 사용하였다. 본 실험동물에서의 적절한 모델을 구축하기 위하여 Porsolt 등의 강제수영시험을 다소 변형하여 각각의 실험 대상군에 적용하였다. 강제수영시험으로 인한 면역 매개변수의 변화를 보기 위하여, 저자들은 anti-rat RBC 항체의 생성, concanavalin 또는 lipopolysaccharide로 유발된 비장세포의 증식과 사이토카인의 유전자 발현 양상을 연구하였다. 결과 : Paroxetine과 sertraline은 모두 투여량에 따라 마우스의 부동자세 시간을 감소시켰다. 강제수영시험을 수행한 마우스는 비세포의 유사분열 반응이 의미 있게 감소되었고, anti-rat RBC 항체는 약간 증가하였다. 이러한 모든 반응은 paroxetine에 의해 의미 있게 감퇴되었고. sertraline에 의해 약간 감퇴되었다. 강제수영시험을 시행한 마우스에서 Con-A로유발된 비세포는 강제수영을 시행하지 않았던 정상대조군보다 IL-4의 강한 발현과 IL-2의 약화된 발현을 보였고, IFN-$\gamma$나 lymphotoxin의 발현은 차이가 없었다. IL-6과 IL-10은 양 군 모두에서 발현되지 않았다. 마우스에서 paroxetine과 sertraline의 전처치는 강제수영으로 인한 사이토카인 발현의 변화를 감퇴시켰다. 그렇지만 선택적 세로토닌 재흡수 차단제가 전처치된 마우스에서는 강제수영군에서 발현되지 않았던 IL-6과 IL-10의 발현이 약간의 변화를 보였다. 결론 : 강제수영시험을 시행한 마우스에서 paroxetine과 sertraline의 전처치는 강제수영시험으로 유발된 행동 및 면역능의 변화를 감퇴시켰다. 이러한 선택적 세로토닌 재흡수 차단제는 사이토카인 유전자 발현 특히 IL-6과 IL-10의 유도를 통하여 면역 체계에 모종의 조절 효과를 발휘하는 것으로 추정되었다.

• Journal of Korean Biological Nursing Science
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• 제17권1호
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• pp.37-43
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• 2015

Purpose: Stress, depending on its intensity and duration, results in either adaptive or maladaptive physiological and psychological changes in humans. Also, it was found that stressful experiences increase the signs of behavioral despair in rodents. On the other hand, exercise and melatonin treatment is believed to have many beneficial effects on health. Thus, this study was designed to evaluate the anti-depressant effects of physical activity and melatonin against chronic stress-induced depression in rats. Methods: Adult male Sprague-Dawley(SD) rats(200-250g, 7 weeks of age) were subjected to depression induced by chronic stress. Chronic depression was induced with forced-swim stress (FSS) and repeated change of light-dark cycle for 4 weeks. In the last 2 weeks, some rats were confined in a cage enriched with a running wheel, seesaw and chewed a ball from 19:00 to 07:00 every day. Melatonin was injected intra-peritoneally (I.P), and the rats received intraperitoneal injections of melatonin (15 mg/kg). The Forced Swim Test (FST) was performed to evaluate the immobility behaviors of rats for a 5 min test. Results: It was found that, the immobility time in FST was significantly (p<.05) lower in physical exercise ($M=58.83{\pm}22.73$) and melatonin ($M=67.33{\pm}37.73$) than in depressive rats ($M=145.93{\pm}63.16$) without physical activity. Also, TPH positive cell in dorsal raphe was significantly (p<.05) higher in exercise ($M=457.38{\pm}103.21$) and melatonin ($M=425.38{\pm}111.56$) than in depressive rats ($M=258.25{\pm}89.13$). Conclusion: This study suggests that physical activity and melatonin produces antidepressant-like effect on stress-induced depression in rats. So, physical exercise and melatonin may be a good intervention in depression patients.

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.31-44
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• 2008

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity. Although it has been shown that lateral septum is involved with the FST-related behavior, it is not clear whether antidepressant treatments could alter the FST-induced gene expression profile in the lateral septum. In the present study, the gene expression profiles in response to FST and reboxetine pretreatment were observed in the lateral septum of rats. Reboxetine is known as a most selective serotonin norepinephrine reuptake inhibitor. In addition, we compared the changes in gene expression profile between reboxetine response and nonresponse groups, which were determined by counting FST-related behavior. After FST, lateral septum from controls and reboxetine pretreated group were dissected and gene expression profiles were assessed using an Affymetrix microarray system containing 15,923 genes. Various genes with different functions were changed in reboxetine response group compared with reboxetine nonresponse group, In particular, pleiotrophin, orexin receptor 2, serotonin 2A receptor, neuropeptide Y5 receptor and thyroid hormone receptor $\beta$ were decreased in reboxetine response group, but Lim motif-containing protein kinase 1 (Limk1) and histone deacetylase 1 (HDAC1) were increased. Although further studies are required for direct roles of these genes in reboxetine response, the microarray may provide tools to find out potential target genes and signaling pathways in antidepressant response.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.365-369
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• 2014

Cedrus deodara (Pinaceae) has been used traditionally in Ayurveda for the treatment of central nervous system disorders. 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) was isolated from heart wood of Cedrus deodara and was shown to have antiepileptic and anxiolytic activity. Thus, the present study was aimed to explore its anti-depressant effect and to correlate the effect with serotonin and nor adrenaline levels of brain. Albino mice were used as experimental animal. Animals were divided in to three groups; vehicle control, imipramine (30 mg/kg i.p.), BDFD (100 mg/kg i.p.). Tail suspension test (TST) and forced swim test (FST) was performed to evaluate antidepressant effect of BDFD. BDFD (100 mg/kg, i.p.) showed a significant decrease in immobility time when subjected to FST whereas immobility time was not significantly altered in TST. BDFD treatment increased serotonin and noradrenaline levels in the brain which is indicative of BDFD having possible atypical antidepressant action.