Anti-anxiety Effects Research Articles

The Effect of N-acetylcysteine on Alprazolam Withdrawal Symptoms in Wistar Male Albino Rats

Introduction: Alprazolam is a benzodiazepine drug that is mainly used to treat generalized anxiety disorder and sleep disorders. Doctors' insistence on prescribing alprazolam due to its long half-life (16 hours) can lead to severe withdrawal complications. The aim of this study was to evaluate the effect of N-acetylcysteine (NAC) as an antioxidant drug on reducing the withdrawal symptoms of alprazolam in male albino rats. Material and Methods: In this experimental study, 50 albino male Wistar rats were used. 10 rats received normal saline by gavage for 26 days (sham), the rest of the rats received 1 mg / kg of alprazolam daily for 21 days and after drug dependence were randomly divided into 4 groups were divided. The negative control group received normal saline by gavage daily for up to 4 days after the dependence period. The treated groups also received 100, 200, and 400 mg / kg NAC orally for 4 days after the dependence period, after which the anti-anxiety and restless effects of N-acetylcysteine were assessed by behavioral test (Elevated plus-maze test). Results: The variables OAE (p = 0.18), CAE (p = 0.88), CAT (p = 0.53) and OAT percent (p = 0.29) did not show a significant difference between the 5 treatment groups; But OAT (p = 0.07) and OAE_percent (p = 0.001) showed a significant difference between the 5 treatment groups (p <0.05). Conclusion: Due to the antioxidant properties of NAC and its ability to counteract oxidative stress in the nervous system, it can be used to control the symptoms of withdrawal syndrome in people with a history of alprazolam dependence. In the present study, a dose of 400 mg / kg NAC had the best therapeutic effects in rats. In future studies, it is recommended to obtain an appropriate dose for people who experience symptoms of alprazolam withdrawal syndrome.

Cheonwangbosimdan mitigates post-traumatic stress disorder-like behaviors through GluN2B-containing NMDA receptor antagonism in mice

Ethnopharmacological relevanceCheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects. Aim of the studyThe purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study. Materials and methodsA single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors. ResultsCWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction. ConclusionsCWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies.

The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/β-Catenin Signaling

Defective β-catenin signaling is accompanied with compensatory neurogenesis process that may pave to anxiety. β-Catenin has a distinct role in alleviating anxiety in adolescence; however, it undergoes degradation by the degradation complex Axin and APC. Vilazodone (VZ) is a fast, effective antidepressant with SSRI activity and 5-HT1A partial agonism that amends somatic and/or psychic symptoms of anxiety. Yet, there is no data about anxiolytic effect of VZ on anxiety-related neurogenesis provoked by stress-reduced β-catenin signaling. Furthermore, females have specific susceptibility toward psychopathology. The aim of the present study is to uncover the molecular mechanism of VZ relative to Wnt/β-catenin signaling in female rats. Stress-induced anxiety was conducted by subjecting the rats to different stressful stimuli for 21 days. On the 15th day, stressed rats were treated with VZ(10 mg/kg, p.o.) alone or concomitant with the Wnt inhibitor: XAV939 (0.1 mg/kg, i.p.). Anxious rats showed low β-catenin level turned over by Axin-1 with unanticipated reduction of APC pursued with elevated protein levels of neurogenesis-stimulating proteins: c-Myc and pThr183-Erk likewise gene expressions of miR-17-5p and miR-18. Two weeks of VZ treatment showed anxiolytic effect figured by alleviation of hippocampal histological examination. VZ protected β-catenin signal via reduction in Axin-1 and elevation of APC conjugated with modulation of β-catenin downstream targets. The cytoplasmic β-catenin turnover by Axin-1 was restored by XAV939. Herein, VZ showed anti-anxiety effect, which may be in part through regaining the balance of the reduced β-catenin and its subsequent exaggerated response of p-Erk, c-Myc, Dicer-1, miR-17-5p, and miR-18.Graphical

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway

Ethnopharmacological relevanceRosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. Aim of the studyThe aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. Materials and methodsGas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. ResultsREO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. ConclusionsThis study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

The effect of lavender on mood disorders associated with the use of combined oral contraceptives (COCs): a triple-blinded randomized controlled trial

BackgroundThe use of contraceptive methods is influenced by their effectiveness, availability, and minimal side effects. OCPs are one of the most effective and widely used methods of pregnancy prevention worldwide. This method not only prevents pregnancy but also helps prevent and treat other diseases. One of the main reasons for discontinuing this method is the emotional disturbances associated with its use. Lavender is an evergreen, fragrant plant that has gained significant attention for its anti-anxiety effects. This study was conducted to investigate the effect of lavender essential oil capsules on mood disorders during the use of COCs.MethodsThis triple-blinded clinical trial was conducted on 60 married women (aged 15–49 years old) who were consumers of COCs, referring to 26 health centers in Tabriz, Iran. The participants were randomly assigned to either the intervention (consuming one gelatin capsule containing 80 mg LEO daily) or control (consuming one placebo capsule daily) group. The intervention continued for 56 days. Scores for positive and negative were determined using the Positive and Negative Affect Schedule (PANAS) questionnaire; and for stress, depression, and anxiety were measured using the DASS-21 questionnaire on day’s 28th and 56th post-intervention. Data analysis was conducted using the t-test and ANOVA with repeated measures, and a p-value of < 0.05 was considered significant for all analyses.ResultsA statistically significant difference was observed in mood disorders, stress, and depression between women receiving LEO or placebo. The consumption of LEO increased the positive mood on day 28 [MD (95% CI): 4.5 (2.1 to 7.0), p = 0.001] and day 56 [5.9 (3.4 to 8.3), p < 0.001] while decreased the negative mood on day 28 [MD (95% CI): -3.5 (-5.3 to -1.3), p < 0.001] and day 56 [-4.3 (-6.3 to -2.2), p < 0.001], stress on day 28 [MD (95% CI): -4.9 (-7.1 to -2.8), p = 0.001] and day 56 [-5.3 (-7.6 to -3.1), p < 0. 001], and depression on day 28 [MD (95% CI): -3.0 (-4.9 to 1.1), p = 0.003] and day 56 [-3.1 (-5.0 to 1.2), p = 0.002]. There was no statistically significant difference between the two groups in terms of anxiety.ConclusionsThe consumption of LEO with COCs improved mood disorders and reduced stress and depression. The use of hormonal contraceptives and mood changes should be considered by providers. Therefore, regarding the possibility of mood changes, it is expected that appropriate counseling and education will be provided to women who consume COC., providing appropriate solutions, including the simultaneous use of LEO.

Glycyrrhizic acid treatment ameliorates anxiety-like behaviour via GLT1 and Per1/2-dependent pathways

Ethnopharmacological relevanceAs a traditional Chinese medicinal herb, Glycyrrhiza. UralensisFisch. (licorice root, chinese name: Gancao) has a variety of medicinal values and is widely used clinically. Its main active ingredient, glycyrrhizic acid (GA), is believed to have a neuroprotective effect. However, the underlying biological mechanisms of GA on stress-induced anxiety disorders are still unclear. Aim of the studyTo investigate the anti-anxiety effect of GA and its underlying mechanism. MethodsWe selected the anxiety model induced by repeated chronic restraint stress (CRS) for 2 h on each of 7 consecutive days. GA (4, 20, 100 mg/kg) was injected intraperitoneally once daily for 1 week. The potential GA receptors were identified using whole-cell patches and computer-assisted docking of molecules. High-throughput RNA sequencing, adeno-associated virus-mediated gene regulation, Western blotting, and RT-qPCR were used to assess the underlying molecular pathways. ResultsGA alleviate depression-like and anxiety-like behaviors in CRS mice. GA decreased synaptic transmission by facilitating glutamate reuptaking in mPFC. Meanwhile, long-term GA treatment increased the expression of clock genes Per1 and Per2. Suppressing both Per1 and Per2 abolished the anxiolytic effects of GA treatment. ConclusionOur study suggests that GA may be developed for the treatment of stress-induced anxiety disorders, and its mechanism is related to GLT1 and Per1/2-dependent pathways. This presents a novel approach to discovering potent therapeutic drugs.

The gut microbiome modulates the susceptibility to traumatic stress in a sex-dependent manner.

Post-traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats. Here, we utilized the single prolonged stress animal model and employed unsupervised machine learning to classify stressed animals into stress-susceptible subgroups and stress-resilient subgroups. Subsequently, using 16S V3-V4 rDNA sequencing, we investigated the differential gut microbiota alterations between susceptible and resilient individuals in male and female rats. Our findings revealed distinct changes in gut microbiota composition between the sexes at different taxonomic levels. Furthermore, the abundance of Parabacteroides was lower in rats that underwent SPS modeling compared to the control group. In addition, the abundance of Tenericutes in the stress-susceptible subgroup was higher than that in the control group and stress-resilient subgroup, suggesting that Tenericutes may be able to characterize stress susceptibility. What is particularly interesting here is that Cyanobacteria may be particularly associated with anti-anxiety effects in male rats. This study underscores sex-specific variations in gut microbiota composition in response to stress and sex differences should be taken into account when using macrobiotics for neuropsychiatric treatment, highlighting potential targets for PTSD therapeutic interventions.

Anti-anxiety and Hypnotic Effects of Lawsonia inermis Hydroalcoholic Extract

Background: Sleep is a vital biological feature, and insomnia causes maladaptive physical and psychological functions. The main flaws of current insomnia medications are significant side effects. A suitable substitute can be herbal products. We aimed to evaluate the anti-anxiety, sleep-inducing, and - prolonging effects of Lawsonia inermis extract and fractions in mice. Methods: Male albino mice were pretreated intraperitoneally (i.p.) with either three doses (40, 80, and 160 mg/kg) of L. inermis extract or n-butanol fraction (NBF), ethyl acetate fraction (EAF), and water fraction (WF), 30 minutes before i.p. injection of 30 mg/kg pentobarbital. Sleep latency and duration of sleep were recorded. For anxiolytic activity, elevated plus-maze (EPM) tests were used. Moreover, the toxicity of the extract was determined in both in vivo and in vitro experiments. Results: L. inermis extract (160 mg/kg) significantly reduced sleep latency and increased sleep duration. EAF at 160 mg/kg decreased sleep latency and increased sleep duration. Flumazenil reversed the hypnotic effect of L. inermis extract (160 mg/kg). L. inermis extract (80, 160 mg/kg) increased the time spent and the number of entries in the open arms of EPM. The tested extracts and fractions administration found no adverse effects on PC12 cell viability. The LD50 was 2.4 g/kg. Conclusion: L. inermis extracts exhibit anxiolytic and hypnotic effects, probably modulating the GABAergic system.

Antianxiety effect of cardamom oil against sleep deprivation-induced anxiety in mice

Abstract BACKGROUND: Sleep is the restorative mechanism involved in the maintenance of physiological and psychological balance. Anxiety is recognized as a typical outcome of sleep deprivation (SLD) that interferes with the normal daily life of the person. The present study was designed to assess the antianxiety effects of cardamom oil in mice subjected to sleep deprivation (SLD)-induced anxiety and to explore possible underlying mechanisms for this activity. METHODS: Cardamom oil (140, 280, and 560 µL/kg intraperitoneal [i.p.]) and midazolam (8 mg/kg i.p.) were administered daily to different groups of mice for 15 consecutive days to sleep-deprived mice. anxiety-like behavior was induced by 48 h of SLD, and the antianxiety activity was evaluated using the elevated plus maze (EPM) test, light–dark, hole board, and marble-burying models. RESULTS: Cardamom oil significantly diminished the SLD-induced anxiety-like behaviors in mice as indicated by increased time spent in open arms (EPM), average time spent in lit box (light–dark model), number of head dips (hole board) and decreased number of marbles buried (marble-burying model) as compared to SLD animals. In biochemical studies, chronic administration of cardamom oil significantly increased γ-amino butyric acid (GABA), serotonin (5-HT), reduced glutathione (GSH), and catalase levels, while decreasing lipid peroxidation. CONCLUSION: Both behavioral and biochemical results revealed the protective effect of cardamom oil against SLD-induced anxiety. The underlying mechanism of action appears to involve the enhancement of GABAergic and serotoninergic neurotransmission, as well as the antioxidant properties of cardamom oil.

Beneficial Effects of Acupuncture for Depression-A Possible Mediation of Peripheral Sensory Stimulation and Central Oxytocin Release

In modern society, depression is one of the most common mental disorders. It is generally thought that depression is due to the disorders of neuronal circuits and chemical balance in the brain. Patients with depression often receive treatment with selective serotonin reuptake inhibitors (SSRIs). However, recent studies suggest that the magnitude of benefit of pharmacological treatment is quite limited for these patients. Although recent studies propose acupuncture as a non-pharmacological approach to managing depression, the mechanism of its beneficial effects is not well understood. Somatosensory pathways stimulated by acupuncture relay to the central nervous system (CNS). In animal studies, acupuncture has demonstrated the potential to ameliorate neural abnormalities associated with depression. As complex daily life stress is highly associated with depression, the procedure that suppresses stress responses would be a good candidate to treat depression. Oxytocin (OXT) is a hormone produced at the hypothalamus and mediates social bonding and stress reduction. OXT inhibits stress-induced corticotropin-releasing factor (CRF) expression at the hypothalamus, resulting in anti-stress and anti-anxiety effects. Research has demonstrated that acupuncture stimulates the release of hypothalamic OXT through somatosensory stimulation. Thus, stress-related mental disorders can be treated, at least in part, by acupuncture. It is proposed that somatosensory stimulations induced by acupuncture are a possible candidate as a non-pharmacological approach for depression.

Neuronal nicotinic acetylcholine receptor of the central amygdala modulates the ethanol-induced tolerance to anxiolysis and withdrawal-induced anxiety in male rats.

The nicotine acetylcholinergic receptor (nAchR) in the central nucleus of the amygdala (CeA) is known to modulate anxiety traits as well as ethanol-induced behavioral effects. Therefore, the present study investigated the role of CeA nAChR in the tolerance to ethanol anxiolysis and withdrawal-induced anxiety-related effects in rats on elevated plus maze (EPM). To develop ethanol dependence, rats were given free access to an ethanol-containing liquid diet for 10 days. To assess the development of tolerance, separate groups of rats were challenged with ethanol (2 g/kg, i.p.) on days 1, 3, 5, 7 and 10 during the period of ethanol exposure, followed by an EPM assessment. Moreover, expression of ethanol withdrawal was induced after switching ethanol-dependent rats to a liquid diet on day 11, and withdrawal-induced anxiety-like behavior was noted at different post-withdrawal time points using the EPM test. The ethanol-dependent rats were pretreated with intra-CeA (i.CeA) (bilateral) injections of nicotine (0.25 µg/rat) or mecamylamine (MEC) (5 ng/rat) before the challenge dose of ethanol on subthreshold tolerance on the 5th day or on peak tolerance day, that is, 7th or 10th, and before assessment of postwithdrawal anxiety on the 11th day on EPM. Bilateral i.CeA preadministration of nicotine before the challenge dose of ethanol on days 5, 7 and 10 exhibited enhanced tolerance, while injection of MEC, completely mitigated the tolerance to the ethanol-induced antianxiety effect. On the other hand, ethanol-withdrawn rats pretreated i.CeA with nicotine exacerbated while pretreatment with MEC, alleviated the ethanol withdrawal-induced anxiety on all time points. Thus, the present investigation indicates that stimulation of nAChR in CeA negatively modulates the ethanol-induced chronic behavioral effects on anxiety in rats. It is proposed that nAChR antagonists might be useful in the treatment of alcohol use disorder and ethanol withdrawal-related anxiety-like behavior.

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats.

Alteration of gut microbiota and microbial metabolites such as short-chain fatty acids (SCFAs) coexisted with stress-generated brain disorders, including depression. Herein, we investigated the effect of SCFAs in a treatment-resistant depression (TRD) model of rat. Rats were exposed to chronic-unpredictable mild stress (CUMS) and repeated adrenocorticotropic hormone (ACTH) injections to generate a TRD-like phenotype. The cecal contents of these animals were engrafted into healthy-recipient rats and allowed to colonize for 4 weeks (TRD-FMT group). Blood, brain, colon, fecal, and cecal samples were collected for molecular studies. Rats exposed to CUMS + ACTH showed TRD-like phenotypes in sucrose-preference (SPT), forced swim (FST), and elevated plus maze (EPM) tests. The TRD-FMT group also exhibited anxiety- and depression-like behaviors. Administration of SCFAs (acetate, propionate, and butyrate at 67.5, 25, and 40 mM, respectively) for 7 days exerted robust antidepressant and antianxiety effects by restoring the levels of SCFAs in plasma and fecal samples, and proinflammatory cytokines (TNF-α and IL-6), serotonin, GABA, norepinephrine, and dopamine in the hippocampus and/or frontal cortex of TRD and TRD-FMT animals. SCFAs treatment elevated the expression of free-fatty acid receptors 2/3, BDNF, doublecortin, and zonula-occludens, and reduced the elevated plasma levels of kynurenine and quinolinic acid and increased mucus-producing goblet cells in TRD and TRD-FMT animals. In 16S sequencing results, decreased microbial diversity in TRD rats corresponds with differences in the genus of Faecalibacterium, Anaerostipes, Allobaculum, Blautia, Peptococcus, Rombustia, Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-002, Solobacterium, Subdolibacterium, and Eubacterium ventriosum. SCFAs may impart beneficial effects via modulation of tryptophan metabolism, inflammation, neurotransmitters, and microbiota-gut-brain axis in TRD rats.

Linderane Attenuates Complete Freund's Adjuvant-Induced Pain and Anxiety in Mice by Restoring Anterior Cingulate Cortex Microglia M2 Polarization through Activating Cannabinoid 2 Receptor.

Chronic pain is a common condition that causes negative emotions as the disease progresses. The anterior cingulate cortex (ACC) is a key region in the integration of nociceptive perception and emotional response in chronic pain. Linderane (LDR) is an active ingredient from Linderae radix, a traditional Chinese medicine with anti-inflammatory, analgesic, and antibacterial properties. In this study, the analgesic and antianxiety effects of LDR were evaluated using a complete Freund's adjuvant (CFA)-induced inflammatory pain model in C57BL/6 male mice. Mechanical and thermal pain sensitivity were measured through plantar mechanical analgesia and hot plate apparatus, and anxiety-like behavior was evaluated by open field and elevated plus maze tests. The results showed that LDR-alleviated CFA-induced pain and anxiety, reduced the release of inflammatory cytokines, and inhibited ACC microglial activation. Target prediction, molecular docking, and cellular thermal shift assay demonstrated that LDR could bind to the cannabinoid 2 receptor (CB2R), a key component of the endocannabinoid system with an important role in regulating pain and related emotions. Moreover, both the analgesic effect of LDR and its regulation of microglia polarization were reversed by a CB2R antagonist (SR144528) treatment. Therefore, our results suggested that LDR exerted analgesic effects by regulating microglial polarization in ACC via CB2R activation.

Comparison of the Effects of Aromatherapy With Damask Rose and Chamomile Essential Oil on Preoperative Pain and Anxiety in Emergency Orthopedic Surgery: A Randomized Controlled Trial

PurposePatients who are awaiting emergency surgery experience high levels of anxiety and pain. This study aimed to compare the effects of aromatherapy with damask rose and chamomile essential oil on the preoperative pain and anxiety associated with emergency orthopedic surgery. DesignA parallel-group randomized controlled design was used. MethodsNinety participants were selected and randomly assigned to three groups: the damask rose group (n = 30), the chamomile group (n = 30), and the control group (n = 30). In the damask rose and chamomile groups, three drops of 40% essential of each plant were used for inhalation aromatherapy (three drops every hour for 3 hours) Visual Analog Scales were used to evaluate participants’ pain and anxiety levels at baseline, immediately after the intervention, and 1 hour after the intervention. FindingsThe results of repeated measures Analysis of Variance (ANOVA) showed that both of the intervention groups experienced a decrease in pain and anxiety over time compared to the control group (P < .001). ANOVA results showed that immediately after the intervention, the anxiety level of the damask rose group compared to the chamomile and control groups was significantly lower (P = .01). However, there was no significant difference in terms of anxiety between the damask rose and chamomile groups 1 hour after the intervention (P = .07). ConclusionsThe use of damask rose and chamomile in aromatherapy was found to effectively lower anxiety and pain levels in emergency orthopedic surgery patients. The antianxiety effect of damask rose is faster than chamomile.

Dexmedetomidine nasal administration improves perioperative sleep quality and neurocognitive deficits in elderly patients undergoing general anesthesia

ObjectiveTo investigate the improvement of perioperative sleep quality and neurocognitive impairment in elderly patients under general anesthesia by nasal administration of dexmedetomidine.MethodsOne hundred and twenty patients admitted to our hospital for various laparoscopic elective gynecological surgeries lasting more than 1 h under general anesthesia from July 2021 to March 2023 were selected. All subjects were divided into 3 groups according to the random number table method. From 21:00 to 21:30 every night from one day before to 5 days after surgery, group A was given alprazolam 0.4 mg orally; group B was given dexmedetomidine 1.5ug/kg nasal drip; group C was given saline nasal drip. All subjects were observed for general information, sleep quality, postoperative cognitive function, anxiety status, sleep quality, adverse effects and complication occurrence.ResultsThe difference in general information between the three groups was not statistically significant, P > 0.05; the sleep quality scores of the three groups on admission were not statistically significant, P > 0.05. At the Preoperative 1d, postoperative 1d, 3d and 5d, the RCSQ scores of the subjects in group A and group B were higher than those in groups C, and with the postoperative RCSQ scores of subjects in group B were higher as the time increased; the assessment of anxiety status in the three groups 1d before surgery was not statistically significant, P > 0.05. The cognitive function scores of subjects in the three groups were not statistically significant in the preoperative 1d, P > 0.05. The postoperative 1d (24.63 ± 2.23), 3d (25.83 ± 2.53), and 5d (26.15 ± 2.01) scores of the subjects in group B were higher than those in groups A and C (P < 0.05), and the subjects in group B had better recovery of postoperative cognitive function with increasing time; the occurrence of postoperative delirium (POD) in group B (12.5%) were lower on postoperative 5d than those in groups A (37.5%) and C (32.5%) (P < 0.05). There was no statistical significance in the evaluation of anxiety state of the three groups on the first day before operation (P > 0.05). The scores in group B were lower than those in group C on the postoperative 1d, 3d, 5 d (P < 0.05). The overall incidence of adverse reactions and complications in subjects in group B was 17.5% significantly lower than that in groups A and C (P < 0.05).ConclusionDexmedetomidine can effectively improve the sleep disorder of elderly general anesthesia patients, reduce the damage to their neurocognitive function and the occurrence of POD, effectively reduce the anxiety of patients and the occurrence of adverse reactions and complications, and has better sedative, improve postoperative cognitive function and anti-anxiety effects, with a high drug safety, worthy of clinical application and promotion.

Erucic acid treatment in lipopolysaccharide-induced anxiety and depression using ADMET properties / behaviour paradigms / interleukins pathways in rats

The neuroimmune system plays a vital role in the etiology of anxiety and depression. In the current research, the aim was to investigate erucic acid's ability to counteract depression and anxiety induced by lipopolysaccharide (LPS) in rats. Erucic acid is known to have anti-inflammatory properties, and it was hypothesized that it would be able to reduce the inflammation and stress associated with LPS-induced anxiety and depression. The rats were distributed into five groups (n = 6). The impact of erucic acid with the dose administration of 10 and 20 mg/kg on anxiety depression-like behaviour was studied using the elevated plus maze test, staircase test, marble-burying behaviour, open field test, hyper emotionality, force swimming, and tail suspension test. Also, the biochemical parameters including cytokines i.e., interleukin-6 (IL-6) and IL-10 were performed. Swiss ADME, pkCSM, and ProTox-II served as as an integrated online platform for precise and complete predictions to determine ADME/T properties of erucic acid. LPS significantly increased anxiety and depression-like behaviour in rats. Erucic acid reduced the lengthening in time of immobility on LPS administration in the tail suspension test and forced swim test indicating the antidepressant type of action. Anti-anxiety effects of erucic acid were increased time spent in the open arms in the elevated plus maze test, decreased repetitive behaviors in the staircase test, marble-burying, and hyper emotionality tests. The high LD50 value (1.382) indicates that erucic acid is relatively non-toxic in acute oral exposures in rats. Erucic acid also prevented LPS-induced elevation of IL-6 and restored the IL-10 levels. It was demonstrated that erucic acid significantly attenuates LPS-induced depression and anxiety in rats. These findings suggest that erucic acid has potential antidepressant and anxiolytic effects, possibly through modulation of the neuroimmune system and inflammatory response. Erucic acid may be beneficial for neuropharmacological effects like anxiety and depression. Additionally, erucic acid may have potential benefits in treating other neurological disorders, such as Alzheimer's disease and Parkinson's disease. Further research is needed to better understand the potential therapeutic applications of erucic acid in neurological disorders.

Comparative effectiveness of two different doses of botulinum toxin A for the treatment of mild to moderate depression

ObjectiveBotulinum toxin A has been shown to be effective in managing depression. This study aimed to evaluate the antidepressant and antianxiety effects of two different doses of botulinum toxin A in patients with mild to moderate depression. MethodsA total of 140 patients diagnosed with mild to moderate depression at the Department of Neurology of the Second Affiliated Hospital of Soochow University from September 2020 to September 2021 were enrolled for the study. The patients were allocated into two groups and treated with two different doses of botulinum toxin A (50 units or 100 units). Depression scores (HAMD, HAMA, SDS, and SAS) were evaluated at baseline and 1, 2, 4, 8, and 12 weeks after treatment. ResultsThere was a significant improvement in the depressive and anxiety symptoms following treatment with the botulinum toxin A after 12 weeks compared to the baseline. However, there were no significant differences between the two groups. Further, the factor scores of anxiety/somatization, blocking, sleep disorder, and cognitive disorder were significantly decreased after 12 weeks of treatment with 50 units of botulinum toxin A compared to the baseline (P < 0.05). Further, the factor scores of somatic and mental anxiety were significantly decreased at different time points after treatment with 50 units of botulinum toxin A compared to the baseline (P < 0.05). ConclusionLocal injections of 50 units and 100 units of botulinum toxin A shows equal efficacy. Therefore, 50 units of botulinum toxin A could be used clinically to manage mild to moderate depression.

The Effect of Intraoperative Music on Sedation, Anxiety, and Hemodynamic Responses among Patients Undergoing Lower Segment Cesarean Section under Spinal Anesthesia

Background and Aim: Anxiety levels are high in spinal anesthesia as patients are awake. Sedation has an advantage that patients feel comfortable but if sedative drugs are not used judiciously, they can suppress the cardiovascular and respiratory system, lower core body temperature, or severely lower blood pressure. Music reduces awareness under anesthesia and has antianxiety effects. The effect of music on sedation using bispectral index (BIS) along with anxiety and hemodynamic parameters at different time intervals has been studied. Material and Methods: A hospital-based prospective randomized interventional study was done on 60 patients aged between 18 and 35 years undergoing lower segment cesarean sections. Two groups (music headphones with music and nonmusic headphones without music), each containing 30 subjects, were formed using a simple random technique by the sealed envelope method. The levels of sedation using BIS were measured preoperatively, after giving spinal anesthesia, then every 10 min till the end of surgery. Moreover, hemodynamic parameters were also monitored and recorded preoperatively and every 10 min till the end of surgery. Anxiety was measured using a visual analog score for anxiety preoperatively and postoperatively. Results: The BIS index was significantly lower in the music group compared to the nonmusic group from 20 min after start of surgery to the end of surgery (86.17 ± 4.48 vs. 75.73 ± 3.97, P &lt; 0.001). Anxiety was also significantly lower in the music group than in the nonmusic group (4.03 ± 1.47 vs. 0.50 ± 1.57, P &lt; 0.005). Heart rate (HR) was lower in the music group after 20 min of music therapy compared to the nonmusic group (87.87 ± 11.21 vs. 79.67 ± 6.67, P = 0.004) but there was no statistically significant difference in systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and saturation of oxygen between two groups. Conclusion: Our data showed that intraoperative music listening under regional anesthesia has effect on sedation, anxiety, and physiological variables. Therefore, music therapy can be used as nonpharmacological intervention for reducing anxiety and sedation during surgery.

Investigating anxiolytic effect of intranasal micro emulsion in experimental animal models

This investigation aimed to assess the anxiolytic potential of an intranasal micro emulsion formulation in an experimental model utilizing Swiss Albino Mice. The evaluation of anti-anxiety activity was conducted through the Elevated plus Maze and Open Field tests. In the Elevated plus Maze, parameters such as the total count of arm entries and the duration spent in both open and enclosed arms were meticulously recorded. Similarly, the Open Field tests involved the documentation of entries in the central region, the time spent in the central region, entries into the peripheral zone, and time spent in the peripheral zone. The experimental subjects received treatment with the intranasal micro emulsion formulation at a dosage of 50mg/kg. The results from the Elevated plus Maze exhibited a noteworthy (p&lt;0.01**) augmentation in the quantity of entries and the duration of sojourn within the open arm. Parallelly, the Open Field tests revealed a significant (p&lt;0.01**) escalation in the count of squares traversed and the frequency of crossings. This investigation unequivocally indicated that the intranasal micro emulsion formulation elicited a pronounced anti-anxiety effect in the experimental animal model. This research contributes to the expanding body of knowledge on the potential therapeutic efficacy of intranasal micro emulsion formulations in addressing anxiety-related behaviors, thereby paving the way for further investigations and potential clinical applications.