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The cysteine protease, falcipain-2 is an important drug target in human malaria parasite Plasmodium falciparum. A new series of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives 5(a–t) were designed as per pharmacophoric requirements of falcipain-2 inhibitors using ligand-based approach. The target compounds were synthesized from the key intermediate, 2-(1,4-Diazepan-1-yl)-N-phenylacetamide, by coupling it with appropriate carboxylic acids using carbodiimide chemistry. Structural features of target compounds were characterized by spectral data (1H NMR, and mass) and elemental analyses. The purity of the final compounds was confirmed by HPLC. The compounds were tested for their in vitro falcipain-2 inhibitor activity on recombinant falcipain-2 enzyme. Five compounds 5b, 5g, 5h, 5j, 5k showed good inhibitory activity (>60%), against falcipain-2 at 10 μM concentration, and fifteen compounds showed weak to moderate inhibitor activity. Compound 5g, the most potent compound from this series showed 72% inhibition at 10 μM concentrations. Keywords: Malaria, Plasmodium falciparum, Structure–activity relationships (SARs), Ligand-based drug design, Antimalarial agents

Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

Portuguese Burghers are a minority ethnic community in Sri Lanka who speak an endangered creole language, Sri Lanka Portuguese (SLP). This paper explores the way Portuguese Burgher identities are articulated in their main performance tradition: a syncretic quadrille dance known as káfriinha. This dance is an important social dance which is embedded in the proceedings of wedding celebrations and other formal events and is a prominent expression of Portuguese Burgher identity. As the primary form of Portuguese Burghers' performative expression, káfriinha reflects aspects that are core to their identity including the socialisation of gender roles and the self-definition of their identity. Its groove is arresting to the observer, enduring in its history and catching in its cultural influence—both within Sri Lanka and across the Indian Ocean. In this article I demonstrate how ethnographic analysis of káfriinha is revealing of continuity and change in Portuguese Burgher identity, bringing into focus processes of creolisation and aesthetic (and cultural) value. [ABSTRACT FROM AUTHOR]

Byline: Visakh. Prabhakar, Deepali. Gupta, Prateek. Kanade, Mahesh. Radhakrishnan Diabetes associated depression is a largely understudied field which nonetheless carries a significant disease burden. The very low therapeutic efficacy of [...]

A comprehensive study of song invites a broad range of approaches including but not limited to ethnomusicology, anthropology, sociology, choreology, gesture studies, cognitive science, history, cultural studies, poetry, folklore, literature and linguistics. While the more obvious (and perhaps visible) contributions of linguistics to song are in terms of investigating songtexts, there are also contributions to be made from interactional, multimodal, poetic, performance-based and anthropological approaches to language and from the margins between these approaches and ethnomusicology. In this paper, I argue the case for musicolinguistic and performance-based approaches to song that combine the insights and methods of embodied, interactional and anthropologically grounded linguistics and folklore with rigorous musical analysis and attention to the cultural and wider social and historical context. There is already a broad paradigm of scholarship in this vein and here I attempt to outline the various approaches and the most useful aspects of them for researchers of song. [ABSTRACT FROM AUTHOR]

Musical performances are at the heart of many significant cultural events and often represent and affirm distinct cultural identities. Ethnographic research on music thus provides an important lens through which to understand distinct cultural worlds. In this introductory article we consider the value of research on music—for the communities for whom it is a highly valued form of cultural expression and for the produced understandings of peoples' social worlds. Extending Anthony Seeger's recent flagging of areas for improvement in ethnomusicological research, this special issue is framed in terms of several concerns: engagement with cultural tradition, music and essentialism, and music as sustainability activism. Against the contemporary context in which the COVID-19 pandemic has dramatically altered the ways that musicians can gather and make music together, we consider the question of research on music from interdisciplinary perspectives and the varied positions of researchers, musicians and community members. [ABSTRACT FROM AUTHOR]

Byline: Shvetank. Bhatt, Mahesh. Radhakrishnan, Ankur. Jindal, Thangaraj. Devadoss, Arghya. Dhar Aim: The aim of the study was to evaluate a novel 5 HT [sub]3 receptor antagonist (6g) on chronic [...]

Byline: Yeshwant. Kurhe, Mahesh. Radhakrishnan, Devadoss. Thangaraj, Deepali. Gupta Objective: To investigate the anti-anxiety activity of '6k', a novel 5-hydroxytryptamine type 3 (5-HT [sub]3 ) receptor antagonist in in mice. [...]

Despite sharing some interesting linguistic and possible cultural connections from a very distant past, South Indian and Irish musical cultures have emerged from highly distinct contexts and influences. Drawing on doctoral field research within the respective traditions as practiced in Australia as well as experience as a student and performer, this paper presents a comparison of Carnatic and Sean-nós singing from the perspectives of anthropology, ethnomusicology and linguistics and outlines some significant areas of connection and contrast. This analysis of two diasporic traditions in an antipodean settler context represents an innovative departure, by focusing not on the heartlands of these musical traditions, but on their existence in an urban, transnational context, dominated by an Anglo-Australian majority. Such a comparison reveals differing perspectives on both traditions. [ABSTRACT FROM PUBLISHER]

Objective: In the last few decades, serotonin type-3 (5-HT3) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.]) or diazepam (2 mg/kg, i.p.) or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP) (mCPP, a 5-HT2A/2C receptor agonist, 1 mg/kg, i.p.) and buspirone (BUS, a partial 5-HT1A agonist, 10 mg/kg, i.p.) were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05) increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT3 receptor antagonist with standard anxiolytics may improve therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Aim:To investigate the antidepressant-like effects of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide (6z) in acute and chronic murine models of depression.Methods:5-HT3 receptor antagonism was examined in guinea pig ileum in vitro. A tail suspension test (TST) was used as acute depression model to evaluate the antidepressant-like behavior in mice treated with 6z (0.5-2 mg/kg, ip). In chronic depression model, mice were exposed to a 4-week chronic unpredictable stress (CUS) protocol, and treated with 6z (0.5-2 mg·kg−1·d−1, po) or a positive drug fluoxetine (10 mg·kg−1·d−1, po) in the last 2 weeks, followed by behavioral and biochemical assessments.Results:The 5-HT3 receptor antagonism of 6z (pA2=7.4) in guinea pig ileum was more potent than that of a standard 5-HT3 receptor antagonist ondansetron (pA2=6.9). In acute depression model, 6z administration significantly decreased the immobility duration. In chronic depression model, 6z administration reversed CUS-induced depressive-like behavior, as evidenced by increased immobility duration in the forced swim test and sucrose preference in the sucrose preference test. Furthermore, chronic administration of 6z prevented CUS-induced brain oxidative stress, with significant reduction of pro-oxidant markers and elevation of antioxidant enzyme activity. Moreover, chronic administration of 6z attenuated CUS-induced hypothalamic-pituitary-adrenal axis hyperactivity, as shown by reduced plasma corticosterone levels. Similar results were observed in the fluoxetine-treated group.Conclusion:6z is a novel 5-HT3 receptor antagonist with potential antidepressant-like activities, which may be related to modulating hypothalamic-pituitary-adrenal axis and attenuating brain oxidative damage. [ABSTRACT FROM AUTHOR]

Abstract: Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light–dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system. [Copyright &y& Elsevier]

Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body's reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants. Materials and Methods: In the present study, a novel and potential 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA2 (7.5) values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS)-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. Results: The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05) increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. '6g' (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21 days) signficantly (P < 0.05) reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities). However fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain while '6g' (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05) effect on the nitrite levels in brain. Conclusion: Compound '6g' exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms. [ABSTRACT FROM AUTHOR]

Objectives The inconsistent therapeutic outcome necessitates identifying novel compounds for the treatment of depression. Therefore, the present study is aimed at evaluating the antidepressant-like effects of a novel 5- HT3 receptor antagonist 3-methoxy- N- p-tolylquinoxalin-2-carboxamide ( QCM-4) on chronic unpredictable mild stress ( CUMS) induced behavioral and biochemical alterations in mice. Methods Animals were subjected to different stressors for a period of 28 days. Thereafter, battery tests like locomotor score, sucrose preference test, forced swim test ( FST), tail suspension test ( TST), elevated plus maze ( EPM) and open field test ( OFT) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione ( GSH), catalase and superoxide dismutase ( SOD) were assessed in brain homogenate. Key findings QCM-4 dose dependently reversed the CUMS induced behavioral and biochemical alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the percent time in open arm in EPM and increasing the ambulation along with the rearings and decreased number of fecal pellets in OFT. Further, biochemical alterations were attenuated by QCM-4 as indicated by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD. Conclusions QCM-4 attenuated the behavioral and biochemical derangements induced by CUMS in mice, indicating antidepressant behavior of the novel compound. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-anxiety activity of "6k", a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice. Materials and Methods: Anti-anxiety activity of "6k" (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). Diazepam (2 mg/kg, i.p.) served as reference standard. Results: "6k" significantly (P < 0.05) increased the time and entries in open arm in EPM as compared to vehicle control group. Further, "6k" significantly (P < 0.05) increased the central and peripheral ambulation along with rearings and time in central area; whereas, reduced the fecal pellets in OFT as compared to vehicle control group. There was significant (P < 0.05) reduction in the latency to enter dark chamber; whereas, increased number of crossings and time in light chamber in L&D aversion test by treatment with "6k" as compared to vehicle control group. In HBT, "6k" significantly (P < 0.05) increased the number of head dipping and squares crossed; whereas, reduced the latency for first head dip and number of fecal pellets as compared to vehicle control group. Conclusion: A novel 5-HT3 receptor antagonist has anti-anxiety action. [ABSTRACT FROM AUTHOR]

Background: Depression is a neurological disorder characterized by sad mood, loss of pleasure, agitation and retardation. Though most relevant neuronal pathophysiology is characterized by decrease in monoamine namely; serotonin (5-HT), dopamine, noradrenaline level in central areas regulating mood and behavior, it inadequately explains the exact mechanism involved. Buspirone (BUS), a partial 5-HT1A receptor agonist has shown promising anti-depressant and anxiolytic properties in various pre-clinical and clinical studies, but the molecular and cellular mechanisms are still unclear. Objective: The aim of this study was to investigate, in vivo, the role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in pathophysiology of depression-related disorders and the anti-depressant like activity of BUS. To simulate HPA axis dysregulation, rats were subjected to bilateral adrenalectomy (ADX). Materials and Methods: We have analyzed effect of BUS (10 mg/kg, i.p.) in ADX and sham rats using open field, sucrose consumption, elevated plus maze and hyper-emotionality tests. Results: In all animal models tested, ADX rats exhibited significant depressive and anxiogenic states while BUS was effective in reversing the psychological diseased condition developed. Conclusion: Taken together, these data showed a prominent role of HPA axis in depression and neuronal mechanism of BUS as anti-depressant and anxiolytic agent. Moreover, our findings suggest that BUS can be a better candidate for stress related depression and anxiety. [ABSTRACT FROM AUTHOR]

Depression is among the common psychiatric disorders, therefore the common pathways and pathogenesis associated with depression is required to be studied. In few years, role of 5-hydroxytryptamine-1A/B (5-HT1A/B) receptors in depressive disorders have been revealed. Both preclinical and clinical studies reported that the potential agonist and antagonist at 5-HT1A/B receptors have significant modulatory effects in depression. However, the collective details regarding the involvement of 5-HT1A/B receptors and the molecular pathways associated in depression is lacking. Thus, the present review evidence the link between 5-HT1A/B receptors in the brain and depression, the possible pathways involved and their alterations in depression. Further, it reviews the preclinical evidences of 5-HT1A/B receptor modulators as antidepressant agents and their effectiveness. The current review also details the clinical relevance of 5-HT1A/B receptors etiopathogenesis of major depression in humans. [ABSTRACT FROM AUTHOR]

The article focuses on the importance of graffiti in Cities. It presents a case of Chennai, India. The visual artifacts, already brought to life by and through different intent, have lives of their own. They circulate and produce different meanings according to the world they inhabit and the lives they live. The city is ordered in the map but the contestations within are made visible on streets and spaces through graffiti. The artifacts produced here are creatively innovated and deployed to effect. They blur the boundary of private and public of the city as a space. If a pedigreed art circulates in a legitimate medium, popular culture thrives on the chaos and uses the city as its canvas.

The article offers information on the periodical including members of the editorial board such as Karen B., Kusal Das and Yoram Epstein; a table of content for the issue; and information on manuscript preparation.

Pyridine has been used for one-pot, two-component synthesis of ethyl 3-substituted-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives in moderate to good yields by condensing N-substituted thioureas with diethyl ethoxymalonate under microwave irradiation. [ABSTRACT FROM AUTHOR]

Communicative expertise in the host society's dominant language is central to newcomers' socio-professional integration. To date, SLA research has largely ignored laypeople's perspectives about Lx communicative expertise, though they are the ultimate judges of real-life interactional success. Sociolinguistic studies have shown that laypeople may base their judgments of Lx speech not only on linguistic criteria, but also on extralinguistic factors such as gender and language background. To document laypeople perspectives, we investigated the professional characteristics attributed to four ethnolinguistic groups of French Lx economic immigrants (Spanish, Chinese, English and Farsi) who were nearing completion of the government-funded French language training program in Quebec City, Canada. We asked L1 naïve listeners (N = 49) to evaluate spontaneous speech excerpts, similar in terms of content and speech qualities, produced by a man and a woman from each target group. After they listened to each audio excerpt, we asked listeners to select the characteristics they associated with that person from a list of the most frequent professional qualities found in job advertisements. Data analysis showed that few Lx users were perceived as having strong communication skills in French. Logistic regression revealed no significant relationships between language group, gender, communicative effectiveness, and professional characteristics. However, there were significant associations between communicative effectiveness with the following characteristics: can work independently, can relate to others, is dynamic, has a sense of initiative, and shows leadership skills. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes is a persistent metabolic disorder, which often leads to depression as a result of the impaired neurotransmitter function. Insulin is believed to have antidepressant effects in depression associated with diabetes; however, the mechanism underlying the postulated effect is poorly understood. In the present study, it is hypothesized that insulin mediates an antidepressant effect in streptozotocin (STZ) induced diabetes in mice through modulation of the serotonin system in the brain. Therefore, the current study investigated the antidepressant effect of insulin in STZ induced diabetes in mice and insulin mediated modulation in the brain serotonin system. In addition, the possible pathways that lead to altered serotonin levels as a result of insulin administration were examined. Experimentally, Swiss albino mice of either sex were rendered diabetic by a single intraperitoneal (i.p.) injection of STZ. After one week, diabetic mice received a single dose of either insulin or saline or escitalopram for 14days. Thereafter, behavioral studies were conducted to test the behavioral despair effects using forced swim test (FST) and tail suspension test (TST), followed by biochemical estimations of serotonin concentrations and monoamine oxidase (MAO) activity in the whole brain content. The results demonstrated that, STZ treated diabetic mice exhibited an increased duration of immobility in FST and TST as compared to non-diabetic mice, while insulin treatment significantly reversed the effect. Biochemical assays revealed that administration of insulin attenuated STZ treated diabetes induced neurochemical alterations as indicated by elevated serotonin levels and decreased MAO-A and MAO-B activities in the brain. Collectively, the data indicate that insulin exhibits antidepressant effects in depression associated with STZ induced diabetes in mice through the elevation of the brain serotonin levels. [Copyright &y& Elsevier]

Antimicrobial chemotherapy is the clinical application of antimicrobial agents to treat infectious disease. A new series of 3,6-disubstituted- and 2,3,6-trisubstitutedquinoxalines have been synthesized by appropriate methods. All test compounds have been evaluated for in vitro antimicrobial activity. Further investigation using MIC experiment was performed; It appears that, compound 14c has higher broad-spectrum antibacterial activity (MIC= 0.01–0.24 ug/ml) than the reference drug, streptomycin (MIC= 0.03–0.97 ug/ml). As well, it elicited remarkable antifungal activity than the reference drug clotrimazole against almost all the selected strains. Moreover, docking study of the most active compounds into MurF active site has confirmed their binding affinity to MurF. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Obesity is an important risk factor for depression as more than half of the obese population is susceptible for depression at double rate. Our earlier studies reported the antidepressant potential of 5-HT3 receptor antagonist, ondansetron (OND) in depression associated obesity using behavioral tasks. The present research work is aimed to evaluate the effect of OND on depression associated with obesity with special emphasis on biochemical and molecular mechanisms such as hippocampal brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP), 5-hydroxytryptamine (5-HT), hippocampal histological examination and immunohistochemical expression of p53 proteins. MATERIALS AND METHODS: Mice were fed with high-fat diet (HFD) for 14 weeks, followed by treatment schedule for 28 days with vehicle/OND (0.5 and 1 mg/kg, p.o.)/reference antidepressant escitalopram (10 mg/kg, p.o.). Subsequently, animals were screened in the behavioral tests of depression such as forced swim test (FST) and sucrose preference test (SPT), biochemical estimations including hippocampal cAMP, BDNF and 5-HT, and molecular assays mainly histology and p53 expression of dentate gyrus (DG). RESULTS: HFD-fed mice showed increased immobility time in FST, reduced sucrose consumption in SPT, decreased level of signal transduction factor cAMP, neuronal growth factor BDNF and neurotransmitter 5-HT in the hippocampus, and raised and p53 expression neuronal damage in the DG region of mice fed with HFD in comparison to the mice fed with normal pellet diet. Chronic treatment with OND (0.5 and 1 mg/kg, p.o.) significantly inhibited the behavioral, biochemical and molecular modifications in HFD-fed mice. CONCLUSION: In the preliminary study, OND attenuated depression associated with obesity in mice fed with HFD using various assays procedures, at least in part by the modulation of serotonergic transmission. [ABSTRACT FROM AUTHOR]

Background: Several preclinical studies have shown that serotonergic 5-HT3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound “6n” (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT3 receptor antagonist with an optimal log P (2.52) and pA2 (7.6) value was screened for its neuro-pharmacological potential in chronic rodent models of depression and anxiety named traumatic brain injury (TBI). Methods: In this model, a 1 cm midline scalp incision was made, and the muscles were retracted to expose the skull. A stainless steel disc (10 mm in diameter and 3 mm in depth) was placed centrally between the lambda and bregma regions. The injury was induced using the impact acceleration model of TBI. Specifically, a 400 g metal weight was dropped from a height of 1 m guided by a straight pipe, onto the metal disc placed over the rat’s skull. Results: The behavioral anomalies of the TBI rats were attenuated by the chronic treatment of compound 6n (1 and 2 mg/kg, p.o.; 14 days) as observed by the modified open field test (ambulation, rearing, and fecal pellet), sucrose consumption test (% sucrose consumption), elevated plus maze [% open arm entries [OAE] and % time spent in open arm (TSOA)], and marble burying test (numbers). In addition, 6n also increased the levels of neurotransmitters (norepinephrine and serotonin) and brain derived neurotrophic factor (BDNF) in TBI rats. Conclusions: The result suggests that compound 6n exhibited antidepressant- and anxiolytic-like effects in rodent models of depression and anxiety. [ABSTRACT FROM AUTHOR]

Background: 5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin- 1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and pA2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. Methods: LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. Results: The results showed that LPS induced anxietylike symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPSinduced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. Conclusions: Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain. [ABSTRACT FROM AUTHOR]

Abstracts from the International Brain Injury Association's 11th World Congress on Brain Injury held on March 2-5, 2016 at The Hague World Forum, the Netherlands are presented including "Focal Triphasic Sharp Waves and Spikes in the Electroencephalogram" by Bruce Janati et al, "Positive Sharp Waves in the EEG of Children and Adults" by Bruce Janati et al and "Preoperative Trepanation and Drainage For Acute Subdural Hsematoma" by Guan Jingyu.

Rationale: Olfactory bulbectomy (OBX) is a widely used model for antidepressant screening and known to induce neurodegeneration in several brain areas. Our earlier studies demonstrated that etazolate produced antidepressant-like effects in behavioral despair models of depression; however, the potential role of etazolate on behavior and morphological changes in the hippocampus region along with its underlying mechanism(s) following OBX has not been adequately addressed. Objectives: We evaluated if etazolate could protect against OBX-induced depression-like behavioral deficits and neurodegeneration. The possible underlying mechanism of etazolate in OBX model was also investigated. Methods: The effects of etazolate were measured in a battery of behavioral paradigms, including the forced swim test (FST), sucrose consumption, open arm activity in elevated plus maze (EPM), and hyperemotionality tests. The underlying mechanisms were investigated by measuring serum corticosterone (CORT), cyclic adenosine monophosphate (cAMP), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and oxidative/nitrosative stress (lipid peroxidation and nitrite) levels and antioxidant enzymes, like reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in the hippocampus. Result: OBX rats showed depression-like behavior anomalies in behavioral paradigms. OBX rats also showed high CORT and decreased cAMP, phosphorylated CREB (pCREB), and BDNF levels. Additionally, we found increased oxidative/nitrosative stress and reduced antioxidant enzyme levels in the hippocampus. Histopathological analysis showed morphological changes and neuronal loss in the hippocampus. Etazolate (0.5 and 1 mg/kg) attenuated the OBX-induced behavioral, biochemical, neurobiological, and histopathological alterations. Conclusion: The aforesaid results suggest that etazolate produces an antidepressant-like effect and neuroprotection in OBX, which is possibly mediated by modulating biochemical and neurobiological markers in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: The inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HT3 receptor antagonist (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations. Methods: Animals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate. Results: (4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD. Conclusions: (4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice. [ABSTRACT FROM AUTHOR]

1, 8-naphthyridine-3-carboxylic acid analogs were synthesized and found to possess potential 5-HT3 receptor antagonism as well as antidepressant-like activity. Initially, 5-HT3 receptor antagonism of all the compounds was determined in the form of p A2 value against agonist 2-methyl 5-HT in longitudinal muscle-myenteric plexus preparation from guinea-pig ileum. Among all the compounds tested, compound 7a demonstrated most promising pA2 value of 7.6. Subsequently, all the compounds were evaluated for antidepressant activity using forced swim test and tail suspension test in mice. Compounds 7a, 7d, 7f, 7h, and 7i exhibited significant (p < 0.05) antidepressant-like activity as compound to vehicle-treated group. Importantly, none of the tested compound affected locomotor activity of mice at tested dose levels. [ABSTRACT FROM AUTHOR]

The biological mechanisms that link the development of depression to metabolic disorders such as obesity and diabetes remain ambiguous. In the present study the potential of a selective cyclooxygenase inhibitor celecoxib (15 mg/kg p.o.) was investigated in depression associated with obesity in mice. Behavioral tests used to assess depressive-like behavior were sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM). The basal locomotor score in obese mice was not altered. Furthermore, estimation of biochemical parameters was performed for plasma glucose, total cholesterol, triglycerides and total proteins. Escitalopram (10 mg/kg p.o.) served as reference standard drug. In the results, chronic treatment with celecoxib for 28 days significantly attenuated the behavioral alterations as indicated by increased the sucrose consumption, reduced the immobility time in FST and TST, increased the percent open arm time and entries in EPM in obese mice. In the biochemical parameters celecoxib significantly reversed the increased plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. In conclusion, celecoxib exhibited potential antidepressant-like effect in depression associated with obesity, which to some extent is mediated by reversing the altered plasma glucose in obese mice. [ABSTRACT FROM AUTHOR]

Objective: To investigate the antidepressant-like effect of N-(benzo[d] thiazol-2-yl)-3- ethoxyquinoxalin-2-carboxamide 6k, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist using rodents behavioral battery tests. Materials and Methods: 6k screening was performed with behavioral assays for depression-like forced swim test (FST) at several single doses (0.25-4 mg/kg, intraperitoneal injection (i.p.)) to test the potency of 6k, in which 2 and 4 mg/kg doses were found to be most effective and hence, in further behavioral assays including mechanistic model like 5-hydroxytryptophan (5-HTP)-induced head twitches was performed in mice at acute doses of 6k (2 and 4 mg/kg, i.p.). Furthermore, olfactory bulbectomy (OBX), a surgical model-induced behavioral alterations was performed in rats, and the effect of 6k administered orally (2 and 4 mg/kg, p.o.) after subchronic treatment for 14 days starting from day 15 of postsurgery was examined by percent sucrose preference test and modified open field test (OFT). Results: 6k (1, 2, and 4 mg/kg, i.p.) reduced the immobility time and increased the swimming behavior in FST without affecting the baseline locomotor score showing antidepressant-like effect. 5-HTP-induced head twitch response was potentiated by 6k (2 and 4 mg/kg, i.p.), which indicated rise in the serotonergic neurotransmission in the brain. 6k (2 and 4 mg/kg, p.o.) showed anti-anhedonia effect by increasing the sucrose consumption and reversed the behavioral alterations when exposed to modified open field in OBX rats after subchronic treatment for 14 days, thus exhibiting antidepressant-like effect. Conclusion: 6k attenuated the behavioral derangement in rodents-based behavioral battery tests for depression, indicating antidepressant-like potential. [ABSTRACT FROM AUTHOR]