GABAergic synapses from the ventral lateral septum to the paraventricular nucleus of hypothalamus modulate anxiety.

Emotional disorders, such as anxiety and depression, represent a major societal problem; however, the underlying neurological mechanism remains unknown. The ventral lateral septum (LSv) is implicated in regulating processes related to mood and motivation. In this study, we found that LSv GABAergic neurons were significantly activated in mice experiencing chronic social defeat stress (CSDS) after exposure to a social stressor. We then controlled LSv GABAergic neuron activity using a chemogenetic approach. The results showed that although manipulation of LSv GABAergic neurons had little effect on anxiety-like behavioral performances, the activation of LSv GABAergic neurons during CSDS worsened social anxiety during a social interaction (SI) test. Moreover, LSv GABAergic neurons showed strong projections to the paraventricular nucleus (PVN) of the hypothalamus, which is a central hub for stress reactions. Remarkably, while activation of GABAergic LSv-PVN projections induced social anxiety under basal conditions, activation of this pathway during CSDS alleviated social anxiety during the SI test. On the other hand, the chemogenetic manipulation of LSv GABAergic neurons or LSvGABA-PVN projections had no significant effect on despair-like behavioral performance in the tail suspension test. Overall, LS GABAergic neurons, particularly the LSv GABAergic-PVN circuit, has a regulatory role in pathological anxiety and is thus a potential therapeutic target for the treatment of emotional disorders.

Unconscious Integration of Categorical Relationship of Two Subliminal Numbers in Comparison with "5".

Many studies have shown that the brain can process subliminal numerals, i.e., participants can categorize a subliminal number into two categories: greater than 5 or less than 5. In the context of many studies on the unconscious integration of multiple subliminal stimuli, the issue of whether multiple subliminal numbers can be integrated is contentious. The same-different task is regarded as a perfect tool to explore unconscious integration. In the two experiments reported, we used a same-different task in which a pair of masked prime numbers was followed by a pair of target numbers, and participants were asked to decide whether the two target numbers were on the same (both smaller or larger than 5) or different sides (one smaller, the other larger than 5) of 5 in magnitude. The results indicated that the prime numbers could be categorized unconsciously, which was reflected by the category priming effect, and that the unconscious category relationship of the two prime numbers could affect the judgment on the category relationship of the two target numbers, as reflected by the response priming effect. The duration of the prime-to-target interstimulus interval (ISI) was also manipulated, showing a positive compatibility effect (PCE) of category priming and a negative compatibility effect (NCE) of response priming no matter whether the ISI was short (50 ms) or long (150 ms). The NCE, which occurred when the prime-to-target ISI was relatively short in this study, contradicted the conventional view but was consistent with previous results of unconscious integration based on an attention modulation mechanism. Importantly, this study provided evidence for the still-under-debate issue of numerical information integration.

5-HT1A receptors within the intermediate lateral septum modulate stress vulnerability in male mice.

Chronic stress is a major risk factor for psychiatric disorders. However, certain individuals may be at higher risk due to greater stress susceptibility. Elucidating the neurobiology of stress resilience and susceptibility may facilitate the development of novel strategies to prevent and treat stress-related disorders such as depression. Mounting evidence suggests that the serotonin (5-HT) system is a major regulator of stress sensitivity. In this study, we assessed the functions of 5-HT1A and 5-HT2A receptors within the lateral septum (LS) in regulating stress vulnerability. Among a group of male mice exposed to chronic social defeat stress (CSDS), 47.2% were classified as stress-susceptible, and these mice employed more passive coping strategies during the defeat and exhibited more severe anxiety- and depression-like behaviors during the following behavioral tests. These stress-susceptible mice also exhibited elevated neuronal activity in the LS as evidenced by greater c-Fos expression, greater activity of 5-HT neurons in both the dorsal and median raphe nucleus, and downregulated expression of the 5-HT1A receptor in the intermediate LS (LSi). Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by LSi administration of 8-OH-DPAT, a 5-HT1A receptor agonist. These results indicate that 5-HT1A receptors within the LSi play an important role in stress vulnerability in mice. Therefore, modulation of stress vulnerable via 5-HT1A receptor activation in the LSi is a potential strategy to treat stress-related psychiatric disorders.

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice.

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

Dopamine D2 receptor within the intermediate region of the lateral septum modulate social hierarchy in male mice.

The dopamine (DA) system has long been involved in social hierarchies; however, the specific mechanisms have not been elucidated. The lateral septum (LS) is a limbic brain structure that regulates various emotional, motivational, and social behaviors. DA receptors are abundantly expressed in the LS, modulating its functions. In this study, we evaluated the functions of DA receptors within different subregions of the LS in social dominance using a confrontation tube test in male mice. The results showed that mice living in social groups formed linear dominance hierarchies after a few days of cohousing, and the subordinates showed increased anxiety. Fos expressions was elevated in the entire LS after a confrontation tube test in the subordinates. However, DA neurons were more activated in the dominates within the ventral tegmental area and the dorsal raphe nucleus. Quantitative real-time polymerase chain reaction results showed that D2 receptor (D2R) within the intermediate region of the LS (LSi) were elevated in the subordinate. In the following pharmacological studies, we found simultaneous D2R activation in the dominants and D2R inhibition in the subordinates switched the original dominant-subordinate relationship. The aforementioned results suggested that D2R within the LSi plays an important role in social dominance in male mice. These findings improve our understanding of the neural mechanisms underlying the social hierarchy, which is closely related to our social life and happiness.

5-HT1A receptor in the central amygdala and 5-HT2A receptor in the basolateral amygdala are involved in social hierarchy in male mice.

Most social animals self-organize into dominance hierarchies that strongly influence their behavior and health. The serotonin (5-HT) system is believed to play an important role in the formation of social hierarchy. 5-HT receptors are abundantly expressed in the amygdala, which is considered as the central node for the perception and learning of social hierarchy. In this study, we assessed the functions of various 5-HT receptor subtypes related to social rank determination in different subregions of the amygdala using the confrontation tube test in mice. We revealed that most adult C57BL/6 J male mice exhibited a linear social rank after a few days of cohousing. The tube test ranks were slightly related to anxiety-like behavioral performance. After the tube test, the amygdala and 5-HT neurons in the dorsal raphe nucleus were activated in lower-rank individuals. Quantitative real-time polymerase chain reaction analysis revealed that despite the high expression of 5-HT1A receptor mRNA in the central amygdala (CeA), 5-HT2A receptor mRNA expression was downregulated in the basolateral amygdala (BLA) in higher-rank individuals. The dominant-subordinate relationship between mouse pairs could be switched via pharmacological modulation of these receptors in CeA and BLA, suggesting that these expression changes are essential for establishing social ranks. Our findings provide novel insights into the divergent functions of 5-HT receptors in the amygdala related to social hierarchy, which is closely related to our health and welfare.

Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress.

INTRODUCTION: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. METHODS AND RESULTS: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. CONCLUSIONS: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.

Data on cardiac lncRNA STX18-AS1 expression in developing human hearts and function during in vitro hESC-cardiomyocyte differentiation.

This article presents data concerning STX18-AS1, a long noncoding RNA gene identified from a Genome-wide association study of Atrial Septal Defect (ASD). The data describes its expression patterns in human tissues and functions in regulating cardiomyocyte differentiation in vitro. STX18-AS1 is a lncRNA with a higher abundance in developing tissues, including hearts. Its transcription distribution within the embryonic hearts during key heart septation stages supports STX18-AS1's association with risk SNPs for ASD. The CRISPR stem cell pool in which STX18-AS1 was knocked down, showed reduced CM differentiation efficiency and lower expression of key cardiac transcriptional factors. This indicated its regulative role in supporting the lineage specification from cardiac mesoderm into cardiac progenitors and cardiomyocytes. These data can benefit the understanding of human embryonic heart developmental biology, and the time-course changes of cardiac transcriptional factors during in vitro cardiomyocyte differentiation from human embryonic stem cells.

mGlu2/3 receptors within the ventral part of the lateral septal nuclei modulate stress resilience and vulnerability in mice.

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs' agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.

A novel RNA-mediated mechanism causing down-regulation of insulating promoter interactions in human embryonic stem cells.

The genome-wide promoter interactome is primarily maintained and regulated by architectural proteins such as CTCF and cohesin. However, some studies suggest a role for non-coding RNAs (ncRNAs) in this process. We aimed to characterise the regulatory role of RNA-mediated promoter interactions in the control of gene expression. We integrated genome-wide datasets of RNA-chromatin and promoter-genome interactions in human embryonic stem cells (hESCs) to identify putative RNA-mediated promoter interactions. We discovered that CTCF sites were enriched in RNA-PIRs (promoter interacting regions co-localising with RNA-chromatin interaction sites) and genes interacting with RNA-PIRs containing CTCF sites showed higher expression levels. One of the long noncoding RNAs (lncRNAs) expressed in hESCs, Syntaxin 18-Antisense 1 (STX18-AS1), appeared to be involved in an insulating promoter interaction with the neighbouring gene, MSX1. By knocking down STX18-AS1, the MSX1 promoter-PIR interaction was intensified and the target gene (MSX1) expression was down-regulated. Conversely, reduced MSX1 promoter-PIR interactions, resulting from CRISPR-Cas9 deletion of the PIR, increased the expression of MSX1. We conclude that STX18-AS1 RNA antagonised local CTCF-mediated insulating promoter interactions to augment gene expression. Such down-regulation of the insulating promoter interactions by this novel mechanism may explain the higher expression of genes interacting with RNA-PIRs linked to CTCF sites.

Acupuncture Relieves Opioid-Induced Constipation in Clinical Cancer Therapy - A Meta-Analysis and Systematic Review.

Cancer pain is a common problem in clinical cancer therapy. Opioid analgesia is one of the most effective drugs for pain relief with satisfying performance besides the side effect of opioid-induced constipation (OIC). Acupuncture, as a Chinese traditional non-invasive intervention, has been applied to clinical cancer pain management and functional constipation therapy. However, only a few studies have adopted this treatment for OIC patients. Due to limited numbers of investigated subjects and variability of application methods, including treatment apparatus, acupoints, durations, and sessions, the interpretation of acupuncture's therapy effects from single-site randomized clinical trials (RCT) is limited. Therefore, we conducted a meta-analysis by collecting published data from Pubmed, Embase, Cochrane library, and Web of Science. Five RCTs focusing on the application of acupuncture with or without medication in OIC patients were included. An overall remission rate of 86.8% in the acupuncture-treated group was achieved, higher than the control group (78.9%; RR, 1.10, 95% CI [1.03, 1.18]). The symptom scores, reporting on defecation frequency, defecation straining, abdominal pain, defection time, and stool property, in acupuncture groups were lower than control groups with a standardized mean difference (SMD) of -2.21 [-4.15, -0.27]. The quality of life (QOL) for patients in the acupuncture treated group increased compared to the control group with reduced PAC-QOL scores (SMD, -1.02 [-1.78, -0.26]). Referring to the effects from pure acupuncture treatment (SMD, -0.43 [-0.83, -0.03]), the co-intervention of acupuncture and drugs (SMD, -1.77 [-2.51, -1.02]) improved the life quality of patients more remarkably (P < 0.05). Overall, our data confirmed the therapeutic effects of acupuncture in the treatment of OIC. The co-intervention of acupuncture with drugs improves the outcomes of OIC patients better than a single strategy. Combined therapy with both medicine and acupuncture has insightful potential for future clinical cancer patient management on constipation problems.

Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway.

Studies have found that salidroside, isolated from Rhodiola rosea L, has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced ß-galactosidase (ß-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.

Cerebroprotein Hydrolysate-I Inhibits Hippocampal Neuronal Apoptosis by Activating PI3K/Akt Signaling Pathway in Vascular Dementia Mice.

INTRODUCTION: Vascular dementia (VaD), one of the brain injuries, is difficult to be cured, so it is important to take active neuroprotective treatment after its occurrence. Many studies have shown that apoptosis serves an important role in VaD occurrence; therefore, inhibition of apoptosis may contribute to the recovery of neurological function after VaD occurrence. Cerebroprotein hydrolysate-I (CH-I), a neuropeptide preparation which consists of several amino acids and small molecular peptides as the main active constituent, is extracted using a method similar to cerebrolysin (CBL) which has neuroprotective and neurotrophic effects. METHODS: In the present study, a VaD model which was constructed using bilateral common carotid artery occlusion (BCCAO) in Kunming mice was applied to examine the neuroprotective effects of CH-I. RESULTS: The results show that CH-I treatment could attenuate the decrease of learning and memory ability, cell apoptosis in the hippocampal CA1 region and inhibit the activation of caspase-3 and caspase-9 in VaD mice. Furthermore, CH-I treatment could also upregulate Bcl-2 protein levels and activate PI3K and Akt. DISCUSSION: We speculate that CH-I may induce a neuroprotective effect activating PI3K/Akt signaling pathway in VaD mice.

Cerebroprotein hydrolysate-I protects senescence-induced by D-galactose in PC12 cells and mice.

Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo, CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.

Prevalence and Characteristics of Rheumatoid-Associated Autoantibodies in Patients with COVID-19.

OBJECTIVE: Patients with rheumatic immune diseases were more likely to develop severe or critical COVID-19. We aimed to determine whether rheumatoid factor antibodies were present in COVID patients and the level and type of rheumatoid factor antibodies produced in COVID-19 patients were related to the degree of the patient's condition. The study also aimed to determine the prevalence and characteristics of rheumatoid factor antibodies in patients with COVID-19. METHODS: Sera collected from 129 patients with COVID-19 were tested for rheumatoid factor antibodies by ELISA. Five patients were tracked for several months to monitor dynamic changes of these antibodies. RESULTS: Rheumatoid-associated autoantibodies were detected in 20.16% of patients (26/129) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, IgM-RF was primarily present in critically ill patients, while IgA-RF was mainly present in mild patients. Five patients were able to track for several months to monitor dynamic changes of these antibodies. Rheumatoid factor antibodies peaks in the later phase of the disease and last for longer time. Anti-Jo-1 antibody was found in one of the five patients. CONCLUSION: This was the case series report that rheumatoid-associated autoantibodies are present in patients with COVID-19. The clinical significance of these antibodies was not fully understood and needed further characterization. These autoantibodies are related to the severity of the patient's disease and exist for a long time in the patient's body, while their impact on the patient's health is unknown.

mGlu2/3 receptor in the prelimbic cortex is implicated in stress resilience and vulnerability in mice.

Resilience, referring to "achieving a positive outcome in the face of adversity", is a common phenomenon in daily life. Elucidating the mechanisms of stress resilience is instrumental to developing more effective treatments for stress-related psychiatric disorders such as depression. Metabotropic glutamate receptors (mGlu2/3 and mGlu5) within the medial prefrontal cortex (mPFC) have been recently recognized as promising therapeutic targets for rapid-acting antidepressant treatment. In this study, we assessed the functional roles of the mGlu2/3 and mGlu5 within different subregions of the mPFC in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in mice. Our results showed that approximately 51.6% of the subjects exhibited depression- or anxiety-like behaviors after exposure to CSDS. When a susceptible mouse was confronted with an attacker, c-Fos expression in the prelimbic cortex (PrL) subregion of the mPFC substantially increased. Compared with the resilient and control groups, the expression of mGlu2/3 was elevated in the PrL of the susceptible group. The expression of mGlu5 showed no significant difference among the three groups in the whole mPFC. Finally, we found that the social avoidance symptoms of the susceptible mice were rapidly relieved by intra-PrL administration of LY341495-an mGluR2/3 antagonists. The above results indicate that mGluR2/3 within the PrL may play an important regulatory role in stress-related psychiatric disorders. Our results are meaningful, as they expand our understanding of stress resilience and vulnerability which may open an avenue to develop novel, personalized approaches to mitigate depression and promote stress resilience.

The GABA(B1) receptor within the infralimbic cortex is implicated in stress resilience and vulnerability in mice.

Resilience is the capacity to maintain normal psychological and physical functions in the face of stress and adversity. Understanding how one can develop and enhance resilience is of great relevance to not only promoting coping mechanisms but also mitigating maladaptive stress responses in psychiatric illnesses such as depression. Preclinical studies suggest that GABA(B) receptors (GABA(B1) and GABA(B2)) are potential targets for the treatment of major depression. In this study, we assessed the functional role of GABA(B) receptors in stress resilience and vulnerability by using a chronic unpredictable stress (CUS) model in mice. As the medial prefrontal cortex (mPFC) plays a key role in the top-down modulation of stress responses, we focused our study on this brain structure. Our results showed that only approximately 41.9% of subjects exhibited anxiety- or despair-like behaviors after exposure to CUS. The vulnerable mice showed higher c-Fos expression in the infralimbic cortex (IL) subregion of the mPFC when exposed to a social stressor. Moreover, the expression of GABA(B1) but not GABA(B2) receptors was significantly downregulated in IL subregion of susceptible mice. Finally, we found that intra-IL administration of baclofen, a GABA(B) receptor agonist, rapidly relieved the social avoidance symptoms of the "stress-susceptible" mice. Taken together, our results show that the GABA(B1) receptor within the IL may play an important role in stress resilience and vulnerability, and thus open an avenue to develop novel, personalized approaches to promote stress resilience and treat stress-related psychiatric disorders.

Endoplasmic reticulum stress and autophagy are involved in adipocyte-induced fibrosis in hepatic stellate cells.

Liver fibrosis, with the characterization of progressive accumulation of extracellular matrix (ECM), is the common pathologic feature in the process of chronic liver disease. Hepatic stellate cells (HSCs) which are activated and differentiate into proliferative and contractile myofibroblasts are recognized as the main drivers of fibrosis. Obesity-related adipocytokine dysregulation is known to accelerate liver fibrosis progression, but the direct fibrogenic effect of mature adipocytes on HSCs has been rarely reported. Therefore, the purpose of this study was to explore the fibrogenic effect of adipocyte 3T3-L1 cells on hepatic stellate LX-2 cells. The results showed that incubating LX-2 cells with the supernatant of 3T3-L1 adipocytes triggered the expression of ECM related proteins, such as α-smooth muscle actin (α-SMA), type I collagen (CO-I), and activated TGF ß/Smad2/3 signaling pathway in LX-2 cells. In addition, 3T3-L1 cells inhibited insulin sensitivity, activated endoplasmic reticulum stress and autophagy to promote the development of fibrosis. These results supported the notion that mature adipocytes can directly activate hepatic stellate cells, and the establishment of an in vitro model of adipocytes on HSCs provides an insight into screening of drugs for liver diseases, such as nonalcoholic fatty liver disease.

GABA(B) receptors within the lateral habenula modulate stress resilience and vulnerability in mice.

Resilience means "the ability to withstand or recover quickly in the face of adversity". Elucidating the neural and molecular mechanisms underlying stress resilience will facilitate the development of more effective treatments for stress-induced psychiatric disorders such as depression. The habenular nuclei, which consist of the medial and lateral sub-regions (MHb and LHb, respectively), have been described as a critical node in emotional regulations. GABA(B) receptors play an important regulatory role in habenular activity. In this study, we assessed the functional role of GABA(B) receptors within the habenula in stress resilience and vulnerability by using chronic social defeat stress (CSDS) model in C57BL/6 male mice. Approximately 47.1% of mice exhibited depression- or anxiety-like behaviors after exposure to CSDS. The vulnerable mice presented elevated c-Fos expression in the LHb when confronted with an attacker. On the other hand, the expression of GABA(B) receptors, including both GABA(B1) and GABA(B2) subunits, was significantly down-regulated in the LHb of the susceptible mice. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LHb injection of both baclofen and CGP36216 (a GABA(B) receptor agonist and antagonist respectively). The above results indicated that GABA(B) receptors in the LHb may play an important role in stress resilience and vulnerability, and thus, may be an important therapeutic target for treatments of stress-induced psychiatric disorders.