Reduction In Immobility Research Articles

Effectiveness of a delirium risk assessment and multidisciplinary care approach in reducing delirium incidence among surgical intensive care unit patients: A retrospective pre-post intervention study

BackgroundDelirium is a common complication in intensive care unit (ICU) patients. It can lead to various adverse events. In this study, we investigated the effectiveness of combining the use of the PREdiction of DELIRium (PRE-DELIRIC) model for delirium risk assessment and the use of a multicomponent care bundle for delirium assessment, prevention, and care in terms of reductions in the incidence of delirium among surgical ICU patients. MethodsThis retrospective study included surgical ICU patients who had received PRE-DELIRIC-guided SMART/SmART care (SMART care: SmART bundle plus multidisciplinary team; SmART care: Sleep/sweet sense of home (creating a comforting and restful environment for patients), Assessment (regular and thorough evaluation of patient needs and conditions), Release (revised endotracheal tube care/removal, restraint device care, and immobility reduction for patient comfort), and Time (reorientation of time to optimize patient care schedules) in our hospital between May 2022 and March 2023 (intervention group) and individuals who had received usual care between January 2021 and April 2022 (historical control group). The SmART intervention involves providing care in the following domains: sleep/sweet sense of home, assessment, release, and time. Patients with a PRE-DELIRIC score of >30% received SMART care, which includes multidisciplinary (physicians, pharmacists, respiratory therapists, and physiotherapists) care in addition to SmART care. For the control group, usual care was provided following the guidelines for the prevention and management of pain, agitation, delirium, immobility, and sleep disruption. The primary outcome was delirium incidence during ICU stay, which was assessed using the Intensive Care Delirium Screening Checklist. The secondary outcomes were the duration of ICU stay, rate of unplanned self-extubation, and status of ICU discharge. ResultsThe intervention and control groups comprised 184 and 197 patients, respectively; their mean ages were 63.7 ± 18.4 years and 62.4 ± 19.5 years, respectively. The incidence of delirium was significantly lower (p = 0.001) in the intervention group (22.3%) than in the control group (47.7%). ConclusionOur findings suggest that the PRE-DELIRIC-guided SMART/SmART care intervention is effective in preventing and managing delirium among surgical ICU patients.

Antidepressant-Like Activity and Molecular Docking Analysis of a Sesquiterpene Lactone Isolated from the Root Bark of Ximenia americana (L.).

Depression, a global cause of disability and premature death, is often treated by traditional healers in Africa using medicinal herbs such as Ximenia americana (L.). With recent pharmacological studies showing the potential antidepressant properties of X. americana extract, this study aimed to evaluate the antidepressant-like effects of the compound(s) isolated from X. americana extract using the forced swim test (FST) and tail suspension test (TST) models predictive of depression. The extracts, administered orally within a dose range of 100-400 mg/kg, notably decreased the immobility time in both the FST and the TST. The most significant reduction occurred at the highest dose of 400 mg/kg, with a decrease of 117.66 s in FST and 53.5 s in TST. However, this reduction in immobility was not linked to changes in movements, as observed in an open-field test (OFT), suggesting that the effect of the extracts was not due to activation of locomotion. Subsequently, a sesquiterpene lactone, dehydrocostus lactone (1) was isolated through solubility-based fractionation and column chromatography of the active root bark extract of X. americana. Dehydrocostus lactone (400 mg/kg) demonstrated a 46.50 s reduction in immobility time in the FST, which was comparable to the positive control, imipramine (30 mg/kg). With a highly favorable docking score of -8.365 kcal/mol on an antidepressant target, monoamine oxidase A (MAO-A; pdb ID: 2BXS), dehydrocostus lactone (1) potentially outperforms the standard MAO-A inhibitor drug, isocarboxazid (-5.847 kcal/mol). Dehydrocostus lactone (1) displayed strong interactions involving hydrogen bond and hydrophobic and electrostatic interactions with specific MAO-A binding site residues. These findings highlight that the antidepressant-like activity of X. americana is partly attributed to the presence of dehydrocostus lactone. Additionally, it also supports the traditional medicinal use of the plant for treating depression.

Investigation of the pharmacological characteristics of Sphaeranthus indicus flowers using phytochemical analysis

Although the conventional usage of Sphaeranthus indicus flowers in medicine exists, there is a lack of research on the precise pharmacological characteristics and comprehensive phytochemical composition of its flowers, resulting in a knowledge gap on their whole therapeutic capabilities. The aim of this work is to identify and describe the phytochemicals found in the flowers of Sphaeranthus indicus and assess specific pharmacological effects, such as antioxidant, antibacterial, anti-inflammatory, thrombolytic, antidepressant, and antidiarrheal characteristics. The investigation revealed that the MESIF (methanol extract of S. indicus flowers) showed substantial antioxidant performance (IC50 = 26.33) accompanied by a moderate phenolic content (93.33 ± 1.76). At 250 and 500 µg/ml, the extract exhibited modest to moderate antibacterial sensitivity against many tested pathogens and significantly reduced inflammation by protein denaturation (41.63 ± 0.11 and 70.52 ± 0.20). Furthermore, MESIF exhibited remarkable thrombolytic activity with a statistically significant (***P<0.001) lysis of clots. The extract showed substantial reduction in immobility in both the Forced Swim Test (FST) and Tail Suspension Test (TST) at doses of 200 mg/kg and 400 mg/kg (***p<0.001). It also a showed significant potent antidiarrheal activity (**p<0.01 at 200 mg/kg and ***p<0.001 at 400 mg/kg), effectively reducing diarrheal episodes in the test models. These findings suggest that the MESIF holds potential for developing treatments with antioxidant, antibacterial, anti-inflammatory, thrombolytic, antidepressant, and antidiarrheal effects. Further research is recommended to isolate specific bioactive compounds and elucidate the mechanisms underlying these pharmacological actions.

Resveratrol as an add on therapy to sertraline in animal models of depression

BackgroundSertraline, a selective serotonin reuptake inhibitor, is a leading antidepressant. Resveratrol is a natural polyphenol with diverse biological activities, including antidepressant-like effects. In this study we evaluated the individual and combined antidepressant effects of resveratrol and sertraline alongwith effect of resveratrol on sertraline serum levels. MethodsTail Suspension Test (TST) and Forced Swim Test (FST) were used to study the antidepressant effect in adult male albino mice which were divided into 5 groups. Group 1 was treated with sertraline, group 2 with resveratrol, group 3 and 4 with sertraline (different doses) and resveratrol, and group 5 was given vehicle control only. Serum sertraline levels were estimated by high performance liquid chromatography (HPLC). Mean increase in time to immobility in TST and mean reduction in immobility in FST of the animal(s) were compared. ResultsCombination of sertraline and resveratrol demonstrated the maximum antidepressant effect followed by sertraline and resveratrol only groups. Serum sertraline levels were higher in the combination group as compared to sertraline only group. ConclusionResveratrol demonstrated antidepressant effects in this study and also had an additive effect on the effect of sertraline. It’s addition also increased serum sertraline levels.

Angelica glauca oil exhibits antidepressant-like effect in experimental animals: An in silico, ADMET and in vivo investigation

Angelica glauca is an aromatic plant of the Apiaceae family. Traditionally A. glauca is used to cure several diseases including anxiety and depression. The present investigation is focused on studying the in silico and in-vivo antidepressant potential of A. glauca essential oil (AGEO). The GC-MS analysis was performed on A. glauca root oil to confirm the genuineness of the drug. Compounds viz. alpha phellandrene, limonene, and z-ligustilide obtained through GC-MS analysis were screened for Monoamine oxidase from Aspergillus niger (MAO-N) (PDB: 2vvl) binding through molecular docking studies by using autoDock/Mcule tool. Prediction of ADME and physicochemical properties of above-detected compounds was done by using preADMET tool version 2.0. The antidepressant activity was investigated by the forced swimming method and tail suspension method. The docking studies exhibits that limonene has a maximum affinity for MAO-N, followed by alpha phellandrene and z-ligustilide. It has been observed that upon oral administration of A. glauca oil (250 & 500 µl/kg b.w.) and reference drug selegiline at the dose of (0.2 mg/kg) shows significant (p<0.01) reduction in immobility in rats in both the behavioral models. All the results were compared with the control group and justified by histopathological analysis of the brain. The data obtained from the study suggests the antidepressant-like action of A. glauca root oil and its phytocompounds in the behavioral models of FST and TST in a dose-dependent manner.

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity.

Selective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4-8 weeks of continuous treatment, have impairing side effects and as many as 40% of patients do not respond. Methylone (3,4-methylenedioxy-N-methylcathinone; MDMC, βk-MDMA, M1) is a rapid-acting entactogen that showed significant benefit in a clinical case series of PTSD patients and was well-tolerated in two Phase 1 studies of healthy volunteers. Based on these early observations in humans, in the current study we tested the hypothesis that methylone has antidepressant-like and anxiolytic effects in preclinical tests. For all studies, 6-8-week-old male Sprague Dawley rats (N = 6-16) were used. We employed the Forced Swim Test (FST), a classic and widely used screen for antidepressants, to explore the effects of methylone and to probe dose-response relationships, durability of effect, and potential interactions with combined SSRI treatment. We compared the effect of methylone with the prototypical SSRI fluoxetine. Three doses of fluoxetine (10 mg/kg) given within 24 h before FST testing caused a 50% reduction in immobility compared with controls that lasted less than 24 h. In contrast, a single dose of methylone (5-30 mg/kg) administered 30 min prior to testing produced a rapid, robust, and durable antidepressant-like response in the FST, greater in magnitude than fluoxetine. Immobility was reduced by nearly 95% vs. controls and effects persisted for at least 72 h after a single dose (15 mg/kg). Effects on swimming and climbing behavior in the FST, which reflect serotonergic and noradrenergic activity, respectively, were consistent with studies showing that methylone is less serotoninergic than MDMA. Fluoxetine pretreatment did not change methylone's antidepressant-like effect in the FST, suggesting the possibility that the two may be co-administered. In addition, methylone (5-30 mg/kg) exhibited anxiolytic effects measured as increased time spent in the center of an open field. Taken together, and consistent with initial clinical findings, our study suggests that methylone may have potential for treating depression and anxiety.

Voluntary wheel running promotes resilience to the behavioral effects of unpredictable chronic mild stress in male and female mice

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. Physiological and behavioral evaluations were conducted throughout the stress paradigm to determine if exercise blunts the effects of UCMS. Chronic stress induced voluntary wheel running (VWR) and weight loss in male and female mice. Compared to males, increased VWR was reported in females who also regained their weight lost by the end of the UCMS protocol. Exercise promoted resilience to stress-induced hyponeophagia in the novelty-suppressed feeding test and increased sucrose consumption. Exercise induced a sex-specific reduction in immobility and avoidance behavior in the tail suspension and open field tests and increased exploratory behavior in the light-dark test. These results indicate that exercise can promote resilience to the behavioral effects of chronic stress in males and females, and can affect behavior independent of chronic stress.

Design, synthesis of 1,2,4-triazine derivatives as antidepressant and antioxidant agents: In vitro, in vivo and in silico studies

The novel series of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides (R: 1–12) were designed, synthesized and evaluated for in-vitro and in-vivo antidepressant-like activity. In MAO-A inhibition assay, compound R: 5 and R: 9 displayed most potent activity with IC50 = 0.12 and 0.30 µM. R: 5 and R: 9 were also evaluated for in-vivo antidepressant using FST and TST. In both models, the test samples R: 5 and R: 9 showed noteworthy antidepressant effect. R: 5 showed 46.48 % and 45.96 % reduction in immobility in FST and TST respectively at dosage of 30 mg/kg (p.o). Whereas compound R: 9 reduced the immobility time by 52.76 % and 47.14 % as compared to control in FST and TST, respectively at same dosage. Both the compounds were also tested for behavioural study using actophotometer and grip tests. None of compounds exhibited decrease in locomotor activity. Further, these compounds were subjected to in silico studies to determine their ADME properties along with binding energies and binding orientions. In ADME studies none of the compounds violated the Lipinski rule and all other parameters were also within the acceptable ranges. In docking study R: 5 (-10.7) and R: 9 (-10.4) were also displayed highest docking score. These encouraging results present the pharmacophoric features of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides as interesting lead for further development of new antidepressant drug molecules.

ANTIDEPRESSANT EFFECT OF ETHANOLIC EXTRACT OF MIMOSA PUDICA COMPARED WITH IMIPRAMINE IN MICE MODELS

Background: Depression was considered as mental illness worldwide. Various symptoms observed with depression are loss of interest, sad mood, disturbed sleep, low energy, and loss of appetite. Mimosa pudica is a traditional medicine having various medicinal properties. Imipramine is a tricyclic antidepressant drug used in depression. This study is to evaluate the antidepressant activity of ethanolic extract of M. pudica leaves and imipramine in mice models. Methods: Swiss albino mice weighing 20–25 g of either sex was involved in study. In each study, the animals were divided into five groups (n=6). Drug was administered i.p. and the antidepressant activity was performed using tail suspension test (TST) and forced swim test (FST) in Group 1 – control group, Group 2 received imipramine (10 mg/kg), and Groups 3, 4, and 5 received M. pudica extract of (4, 6, 8 mg/kg). Results: The study shows the significant reduction in immobility in acute and chronic study of TST and FST with M. pudica extract of (6 mg/kg) and imipramine when compared with control and other extracts of M. pudica (4 mg/kg and 8 mg/kg) Conclusions: The study concluded that the ethanolic extract of M. pudica has significant antidepressant activity and can be, further, considered for the treatment of depression.

Adenosine Monophosphate-activated Protein Kinase (AMPK) in serotonin neurons mediates select behaviors during protracted withdrawal from morphine in mice

Serotonin neurotransmission has been implicated in behavior deficits that occur during protracted withdrawal from opioids. In addition, studies have highlighted multiple pathways whereby serotonin (5-HT) modulates energy homeostasis, however the underlying metabolic effects of opioid withdrawal have not been investigated. A key metabolic regulator that senses the energy status of the cell and regulates fuel availability is Adenosine Monophosphate-activated Protein Kinase (AMPK). To investigate the interaction between cellular metabolism and serotonin in modulating protracted abstinence from morphine, we depleted AMPK in serotonin neurons. Morphine exposure via drinking water generates dependence in these mice, and both wildtype and serotonergic AMPK knockout mice consume similar amounts of morphine with no changes in body weight. Serotonergic AMPK contributes to baseline differences in open field and social interaction behaviors and blocks abstinence induced reductions in immobility following morphine withdrawal in the tail suspension test. Lastly, morphine locomotor sensitization is blunted in mice lacking AMPK in serotonin neurons. Taken together, our results suggest serotonergic AMPK mediates both baseline and protracted morphine withdrawal-induced behaviors.

Evaluation of acute oral toxicity, cytotoxicity, antidepressant and antioxidant activities of Japanese mint (Mentha arvensis L.) oil

Menthol-rich essential oil of Mentha arvensis L . (Japanese mint) have been identified as a valuable and new source of natural bioactive compounds with applications not only in industry but also in our daily life. The present study aimed to assess the cytotoxicity, acute toxicity, antidepressant and antioxidant activities of Japanese mint oil (JMO). Brine shrimp lethality assay was performed to investigate cytotoxicity of JMO. The acute toxicity was evaluated by Lorke's method. Forced swimming test (FST) was performed for determining antidepressant property. The antioxidant potentials were performed by DPPH scavenging assay, ferric reducing antioxidant potential (FRAP) and Fe 2+ ion chelating ability methods. In acute toxicity study, JMO showed toxic effects within 5 minutes and estimated LD 50 value was 2070.4 µl/kg body weight after 10 days oral treatment. The brine shrimp lethality assay exhibited concentration–dependent approach and the LC 50 value was determined to be 139.73 l/ml, with lower and upper limits of 82.2428 l/ml and 202.7082 l/ml, respectively. In the FST method, intraperitoneal injections of JMO emulsion at doses of 78l/kg, 156l/kg, and 225l/kg of body weight resulted in a significant (p<0.005) increase in struggling time and a reduction in immobility. This observation had a nearly identical effect to the reference drug. Besides, JMO showed weak antioxidant activity in DPPH assay with an IC 50 of 72.58±6.16387 μl/ml. But in other two methods, it exhibited strong antioxidant abilities whereas 1.4010 μl/ml reducing power for FRAP assay and 66.66% chelating rate for Fe2+ ion chelating ability test at 100 μl/ml concentration. The investigation clearly showed that JMO have significant antidepressant and cytotoxic properties whereas acute toxicity was moderate. Besides, JMO also possess considerable antioxidant activities.

Assessment of the effects of maternal deprivation in offspring treated with ultra-high diluted Zincum metallicum in rats

Introduction: Clinical studies have shown that adverse events in childhood can lead to the development of psychiatric disorders, such as anxiety, in adolescence and adulthood in humans. Manipulations with laboratory animals, such as maternal deprivation (MD), are a source of stress for the offspring and can be a useful tool for the understanding how these events in the early period of development can lead to behavioral changes in adulthood. Studies about the use of homeopathic ultra-high dilutions as tools to minimize stress are found in the literature, i.e. Zincum metallicum is used for the treatment of neurological and behavioral symptoms, including: weakening of intellectual functions with brain and nervous exhaustion, loss of vitality, slow comprehension, memory disorder, general tremor and constant movements. These alterations can be characterized as stress-related phenomena in different species. &#x0D; Aim: The aim of this study was to evaluate the long-term effects of homeopathic treatment in animals subjected to stress in their early days (maternal deprivation). This study was approved by the Ethics Committee of the University of Santo Amaro (UNISA), according to Process number 11/2014.&#x0D; Materials and Methods: In this study, newborn female rats were subjected to maternal deprivation and treated from the 10th day of lactation (PND10) until weaning (PND21). The animals were divided in 4 groups: 8 treated with Zincum metallicum 30 cH (Zn30cH); 8 treated with Zincum metallicum 6 cH (Zn6cH); 8 treated with 10% hydroalcoholic solution (medicines in blind trials, identified by codes); and 8 animals who had neither taken anything (“blank control”) nor experienced deprivation. The animals were weighed weekly, from weaning until the end of the experiment, and evaluated in the Open Field (OF) and in the Plus Maze (PM) devices to measure mobility, emotionality and anxiety, in 3 moments: in PND21 (childhood), during puberty (PND 40) and adulthood (PND75). Data were analyzed statistically by ANOVA, followed by the Bartlett's Test and Bonferroni's Multiple Comparison Test, being p≤0.05. &#x0D; Results and Discussion: In the OF, it was observed reduction of immobility in Zn6cH group (p≤0.05) at PND21. At PND40, the Zn30cH group showed higher activity than the other groups, with increased rearing and decreased immobility (p≤0.05). Finely, at PND75 (adulthood) no change occurred, and Zincum metallicum treated rats presented similar behavior to the undeprived animals. In the PM, at PND21, the Zn30cH treated deprived group showed decrease in the open arm entry and retention period in the Maze, compared to the control undeprived group (p≤0.05). The time in the closed arm was higher than the undeprived control group and the number of head dips was lower (p≤0.05). The PM observation at 45 and 75 days showed no statistical difference among groups. The deprived animals which took Zn30cH obtained the same gain that the undeprived animals did (p≤0.05). Therefore, the deprived animals that presented anxiety during childhood were in accordance to other studies, showing that maternal deprivation is a stress factor that causes anxiety. However, the time of emotional unbalance was shorter in rats treated with Zincum metallicum. &#x0D; Conclusion: Zincum metallicum 30 cH seems to be a potential medicine to manage troubles in the childhood derived from stress caused by maternal deprivation. However, other studies are already underway with male offspring and neurochemical measurements, for a better parameter of results.

Evaluation of antidepressant activity of methanol extract of (A. Rich) Tiegh using acute inflammatory model of depression in Swiss albino mice

Introduction Depression has been a global public health issue for a while now. This has prompted many researches to develop safer and more effective treatment of depressive illness. Cytokines are believed to alter neurochemical and neuroendocrine processes that have wide-ranging effects on physiology and behavior including depression. Tapinanthus globiferus has been reported to be used in the management of depression and many other neuro-psychiatric illnesses. Aim The aim of this study is to evaluate the antidepressant activity of the methanol extract of Tapinanthus globiferus in acute inflammatory model of depression in mice. Methods The phytochemicals present in methanol leaves extract of Tapinanthus globiferus were screened for using simple chemical tests. LD50 of the extract was determined using OECD method. Anti-depressant effect of the extract was evaluated using tail suspension test (TST) and forced swim test (FST), while open field test was used to validate the observed activity of the extract. The levels of inflammatory cytokines and BDNF were assayed using ELISA kits Results Saponins, cardiac glycosides, flavonoids, alkaloids, tannins, steroids and triterpenoids, while anthraquinones were absent in the extract. The median lethal dose (LD50) of the extract was greater than 5000 mg/kg. The extractsignificantly (p<0.05) reduced body temperature of the mice (measured rectally), and at the extract at highest dose, it significantly (p<0.05) reduced immobility time that was comparable to fluoxetine in TST. However, in FST, a significant (p<0.05) reduction in immobility was observed only in the fluoxetine group in comparison to the LPS-only group. Correspondingly, in this study, the mice in the LPS-only group had higher levels of pro-inflammatory cytokines; Interleukin-1 (IL-1) and Interleukin-6 (IL-6), and cortisol compared to extract treated groups while BDNF level was much higher in the extract treated group compared to the LPS-only and Normal saline group. Conclusion The methanol extract of Tapinanthus globiferus possesses antidepressant activity which may involve amelioration of inflammatory response and enhancement of neurotrophic factors in mice. This provides scientific basis for the use of the plant in the management of depression in traditional medicine.

Pharmacological depletion of serotonin and norepinephrine with para-chlorophenylalanine and alpha-methyl-p-tyrosine reverses the antidepressant-like effects of adolescent caffeine exposure in the male rat.

Adolescent exposure to caffeine has been shown to decrease immobility in the forced swim test, suggesting and antidepressant-like effect of caffeine; however, studies have produced different results with regard to caffeine-induced active behaviors. The present study attempted to clarify the possible neurochemical mechanisms of caffeine's action by selectively depleting norepinephrine with alpha-methyl-p-tyrosine or serotonin with para-chlorophenylalanine in two separate experiments and assessing the ability for caffeine to alter anxiety-like and depressive-like behavior. Caffeine-treated adolescent male rats were exposed to caffeine (0.25 g/L) in their drinking water beginning on P28. A-methyl-p-tyrosine, para-chlorophenylalanine, or saline were administered prior to light-dark, open field, and forced swim testing beginning on P45. Caffeine-induced reductions in immobility and increases in swimming in the forced swim test were reversed by both a-methyl-p-tyrosine and para-chlorophenylalanine. Caffeine-induced increases in crosses and rears were reversed by para-chlorophenylalanine but not alpha-methyl-p-tyrosine, whereas caffeine-induced increases in transitions in the LD test were reversed by alpha-methyl-p-tyrosine but not para-chlorophenylalanine. Taken together, these results suggest that caffeine-induced decreases in immobility in male rats requires both norepinephrine and serotonin as depletion of either prevents the induction of immobility by chronic caffeine.

Participation of the nucleus accumbens dopaminergic system in the antidepressant-like actions of a diet rich in omega-3 polyunsaturated fatty acids.

The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.

The antidepressant activity of alcoholic extract of Withania coagulans fruits in Swiss albino mice by tail suspension test

Background: There are many antidepressant drugs used today have the adverse drug reactions. Withania coagulans – a species to be extinct, is not explored much for its effects on mood except in late seventies. As a result, it was thought worthy to explore antidepressant activities of alcoholic extract of W. coagulans fruits in Swiss albino mice (SAM) using tail suspension test (TST). Aim and Objective: This study aims to study the alcoholic extract of W. coagulans fruits’ antidepressant effect in SAM by TST. Materials and Methods: TST was used for evaluating the antidepressant action of W. coagulans fruits alcoholic extract. If the extract had antidepressant action, then it was estimated that the period of mobility would rise and immobility would reduce. This reduction in immobility, if found statistically significant, was considered for antidepressant action. Results: There was statistically substantial (P < 0.001) association observed between alcoholic extract of W. coagulans fruits with depressant action on mood in SAM by TST. Conclusion: The alcoholic extract of W. coagulans fruits did not prove antidepressant action in SAM. On the other hand, it showed depressive effect on the mood in the TST.

Comparison of Therapeutic Benefit of Bupivacaine HCl Transversus Abdominis Plane (TAP) Block as Part of an Enhanced Recovery Pathway versus Traditional Oral and Intravenous Pain Control after Minimally Invasive Colorectal Surgery: A Prospective, Randomized, Double-Blind Trial

Enhanced recovery pathways (ERPs), when combined with transversus abdominis plane (TAP) blocks, have been proven to reduce the length of stay (LOS) and improve quality outcomes. Nonopioid pain management is an essential component of this pathway, leading to a reduction in immobility, postoperative ileus, and an increase in patient satisfaction. TAP block variations have been studied in general and gynecologic surgery. This study evaluates the effectiveness of laparoscopic TAP blocks in conjunction with the benefit of an ERP. One hundred thirty-seven consecutive laparoscopic and robotic-assisted Colorectal Surgery patients received TAP blocks under laparoscopic guidance while under anesthesia, randomized to a placebo, bupivacaine TAP block, or bupivacaine TAP block with an ERP arm of the trial. Patient demographics, operative techniques, and postoperative outcomes were analyzed using statistical analysis software. Our main objective was to determine short-term benefits of TAP blocks on reducing total narcotic consumption. Secondary objectives included effects of TAP blocks on time to ambulation, time to bowel function, and LOS. To isolate the effect of the TAP blocks, no efforts were made to control nursing or patient education in patients managed without an ERP. Of 137 patients, 14 were withdrawn. All cases were elective, with the main diagnosis colon cancer or dysplastic polyps (47.1%). The median age in each group was comparable (P = 0.12), with female majority in both groups (58.5%). Most procedures were segmental colon resections (74.7%). Thirty-one patients received a placebo, 41 bupivacaine TAP, and 51 bupivacaine TAP plus ERP. In terms of primary endpoints, the bupivacaine plus ERP arm used statistically significant less IV narcotics on postoperative day 1 and in total (P = 0.001, P = 0.008). All patients ambulated on average within the first 24 hours postoperatively, with the TAP plus ERP group approximately 0.5 days sooner (P = 0.001). The TAP plus ERP group also had a return of bowel function and LOS approximately 24 hours early (P = 0.001 and P = 0.001). This study shows that a laparoscopically placed bupivacaine TAP block when used as part of an ERP can reduce LOS, postoperative narcotics, time to ambulation and bowel function, and LOS. Defined pain regimens with auxiliary staff teaching can add to the improvement in quality outcomes in laparoscopic colorectal surgery and, with the addition of the TAP block, can add to patient satisfaction and lower hospital costs.

Antidepressant Effects of the Aqueous and Hydroalcoholic Extracts of Salvia mirzayanii and Salvia macrosiphon in Male Mice

Objectives: As some species of the Salvia family have been shown to exert antidepressant-like activity, the aim of this study was to investigate the antidepressant effects of the aqueous and hydroalcoholic extracts of Salvia mirzayanii and Salvia macrosiphon, two endemic species of salvia in Iran. Methods: In total, 148 eight-week-old male albino mice (25-35 g) were used to carry out the forced swimming test. The effects of different doses of the aqueous (100-1800 mg/kg) and hydroalcoholic extracts (75-900 mg/kg) of Salvia mirzayanii and Salvia macrosiphon on immobility, climbing, and swimming behaviors were examined. Fluoxetine and imipramine were used as control drugs. The effects of extracts on locomotor activity were also evaluated. Results: High doses of the aqueous extracts of both plants and hydroalcoholic extract of Salvia mirzayanii produced a significant reduction in immobility and increase in swimming compared to the control group. The hydroalcoholic extract of Salvia macrosiphon did not show any significant effect on immobility and swimming. Only some doses of hydroalcoholic extract of Salvia mirzayanii and aqueous extract of Salvia macrosiphon showed a significant increase in climbing behavior. The aqueous and hydroalcoholic extract of both plants caused a decrease in spontaneous activity. Conclusions: The findings of this study indicated that the aqueous and hydroalcoholic extracts of Salvia mirzayanii and the aqueous extract of Salvia macrosiphon had antidepressant-like activity. In addition, the hydroalcoholic extract of Salvia mirzayanii and the aqueous extracts of Salvia macrosiphon were more effective fractions of these plants. These endemic Iranian Salvia species may have potential therapeutic effects for depression. © 2019, Author(s).

Carbamoylated erythropoietin produces antidepressant-like effects in male and female mice

Major depressive disorder and related illnesses are globally prevalent, with a significant risk for suicidality if untreated. Antidepressant drugs that are currently prescribed do not benefit 30% of treated individuals. Furthermore, there is a delay of 3 or more weeks before a reduction in symptoms. Results from preclinical studies have indicated an important role for trophic factors in regulating behavior. Erythropoietin (Epo), which is widely prescribed for anemia, has been shown to produce robust neurotrophic actions in the CNS. Although Epo's antidepressant activity has been successfully demonstrated in multiple clinical trials, the inherent ability to elevate RBC counts and other hematological parameters preclude its development as a mainstream CNS drug. A chemically engineered derivative, carbamoylated Epo (Cepo) has no hematological activity, but retains the neurotrophic actions of Epo. Cepo is therefore an attractive candidate to be tested as an antidepressant. Objective: To evaluate the antidepressant properties of Cepo in established antidepressant-responsive rodent behavioral assays. Methods: Adult male and female BALB/c mice were used for this study. Cepo (30 μgrams/ kg BWT) or vehicle (PBS) was administered intraperitoneally for 4 days before the test of novelty induced hypophagia and subsequently at five hours before testing in forced swim test (FST), tail suspension test (TST) and open field test (OFT). To obtain mechanistic insight we examined the phosphorylation of the transcription factor cAMP response element binding protein (CREB).Results: Administration of Cepo at 30 μgrams/ kg BWT, for 4 days produced significant reduction in latency to consume a palatable drink in a novel environment in male and female mice. Male BALB/c mice had a significant reduction in immobility in both tail suspension and forced swim tests, and female mice exhibited lower immobility in the forced swim test.

Effects of Camellia Sinensis Extract on Repeated Restraint Stress-Induced Ovariectomized Female Rats.

The mortality of individuals suffering from depression has been increasing, noticeably of postmenopausal women; consequently, their care and treatment are significant to retain a high quality of life. The aim of this study was to examine the effect of Camellia sinensis (CS) on repeated stress-induced changes of the depression related function on the tail suspension test (TST), forced swimming test (FST) in ovariectomized female rats. After behavioral test, we evaluated the changes in the neurotransmitter by measuring the level of dopamine in the nucleus accumbens (NaC) and the serum levels of estrogen and oxytocin. We used 18F-2-fluoro-deoxy-D-glucose positron emission tomography (18F-FDG-PET) to examine the effects of CS on glucose metabolism in ovariectomized rats. Female rats were randomly segregated into three groups. Nor group was considered as nonoperated and nonstressed group, while the control was the ovariectomized and stressed group (OVX+ST), and CS was the ovariectomized, stressed and CS treated group. The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and CS (300 mg/kg, i.p.) was treated 30 min before IMO stress. Significant reduction of immobility in the TST and FST was indicated in rats treatment with CS compared to the control group (OVX+ST). The levels of estrogen in the serum of the Nor and CS groups were significantly elevated compared to the OVX+ST group. Also, CS activated brain glucose metabolism in the cortex. The present findings suggested that CS had antidepressant effectiveness in a menopausal depression animal model. These findings suggest evidence that CS plays a crucial role in stressful situation, providing that CS might be a dependable antidepressant medicine to treat menopausal depression.