Psychosocial stress can cause mental conditions such as depression in humans. To develop drug therapies for the treatment of depression, it is necessary to use animal models of depression to screen drug candidates that exhibit anti-depressive effects. Unfortunately, the present methods of drug screening for antidepressants, the forced-swim test and tail-suspension test, are limiting factors in drug discovery because they are not based on the constructive validity of objective phenotypes in depression. Previously, we discovered that the onset of nest building is severely delayed in mice exposed to subchronic mild social defeat stress (sCSDS). Therefore, a novel paradigm combining acute social defeat stress (ASDS) and the nest-building test (SNB) were established for the efficient screening of drugs for depressive-like symptoms. Since ASDS severely delayed the nest-building process as shown in chronically social defeated mice, we sought to rescue the delayed nest-building behavior in ASDS mice. Injecting a specific serotonin 2a receptor antagonist (SR-46349B), the nest-building deficit exhibited by ASDS mice was partially rescued. On the other hand, a selective serotonin reuptake inhibitor (fluoxetine) did not rescue the nest-building deficit in ASDS mice. Therefore, we conclude that the SNB paradigm is an another potential behavioral method for screening drugs for depressive-like symptoms including attention deficit, anxiety, low locomotion, and decreased motivation.
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http://dx.doi.org/10.1016/j.beproc.2016.12.003 | DOI Listing |
Biomolecules
December 2024
Division of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
Emerging evidence suggests the serine protease, urokinase plasminogen activator (uPA), may play an important role in the modulation of mood and cognitive functions. Also, preliminary evidence indicates that uPA modulates BDNF activity that is known to be involved in the pathogenesis of mood disorders. However, the physiological functions of uPA in specific brain regions for mediating stress-related emotional behaviors remain to be elucidated.
View Article and Find Full Text PDFPsychol Med
January 2025
Department of Psychiatry, Wroclaw Medical University, Pasteura 10 Street, 50-367 Wroclaw, Poland.
Background: Psychotic-like experiences (PLEs) are subclinical phenomena that often precede the onset of psychosis and occur in various mental disorders. Social determinants of psychosis and PLEs are important and have been operationalized within the social defeat (SD) hypothesis. The SD hypothesis posits that low social status and exposure to repeated humiliation can lead to imbalanced dopamine neuron activity, and thus increased risk of psychosis.
View Article and Find Full Text PDFFood Funct
January 2025
Hubei Provincial Engineering and Technology Research Center for Food Ingredients, Hubei University of Arts and Science, Xiangyang, Hubei, PR China.
The gut microbiome has emerged as a growing focus of research and public health interest, leading to the frequent exploration of probiotic dietary supplements as potential treatments for various disorders, such as anxiety and depression. In the present report, changes in inflammation and microbiome composition were assessed in model mice exhibiting depressive-like behaviors that were exposed to the probiotic HBUAS52074. It was found that HBUAS52074 alleviated the severity of depressive-like behaviors while increasing serum 5-HT concentrations.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address:
In recent years, modulation of microglial phenotype transformation has emerged as a promising strategy for treating central nervous system disorders. Aurantii Fructus Immaturus (Zhishi), a traditional Chinese medicine with versatile applications, contains p-Synephrine (p-SYN) as its principal bioactive compound, recognized for its anti-inflammatory efficacy. However, the molecular mechanisms underlying these effects remain unclear.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.
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