Serial changes in anxiety levels related to corticosteroid use: A single-center prospective study.

Patients with autoimmune diseases treated with corticosteroids sometimes display feelings of anxiety regarding corticosteroid use. In this single-center prospective study, we aimed to evaluate the serial changes in anxiety levels related to corticosteroid use in 18 patients with autoimmune diseases. The degree of anxiety toward corticosteroid use was assessed using the visual analogue scale. Comprehension of drug characteristics and use was assessed using the Likert scale. To assess the patients' levels of depression and anxiety we used the State-Trait Anxiety Inventory. These surveys were conducted immediately before the initiation of corticosteroid therapy and just before discharge from the hospital. We observed a decrease in anxiety levels related to corticosteroid use and State-Trait Anxiety Inventory scores before discharge. However, we did not detect a correlation between these score changes. Additionally, we found that patients who had a poor understanding of the drugs showed little or no changes in their anxiety levels related to corticosteroid use at discharge. These results suggest that some aspects of anxiety related to corticosteroids might be groundless and substantiated by assumptions without a complete understanding of corticosteroid functioning. Patient education regarding corticosteroid use may lead to reductions in anxiety levels and improvement in quality of life of the patients.

ZL006 mitigates anxiety-like behaviors induced by closed head injury through modulation of the neural circuit from the medial prefrontal cortex to amygdala.

Closed head injury is a prevalent form of traumatic brain injury with poorly understood effects on cortical neural circuits. Given the emotional and behavioral impairments linked to closed head injury, it is vital to uncover brain functional deficits and their driving mechanisms. In this study, we employed a robust viral tracing technique to identify the alteration of the neural pathway connecting the medial prefrontal cortex to the basolateral amygdala, and we observed the disruptions in neuronal projections between the medial prefrontal cortex and the basolateral amygdala following closed head injury. Remarkably, our results highlight that ZL006, an inhibitor targeting PSD-95/nNOS interaction, stands out for its ability to selectively reverse these aberrations. Specifically, ZL006 effectively mitigates the disruptions in neuronal projections from the medial prefrontal cortex to basolateral amygdala induced by closed head injury. Furthermore, using chemogenetic approaches, we elucidate that activating the medial prefrontal cortex projections to the basolateral amygdala circuit produces anxiolytic effects, aligning with the therapeutic potential of ZL006. Additionally, ZL006 administration effectively mitigates astrocyte activation, leading to the restoration of medial prefrontal cortex glutamatergic neuron activity. Moreover, in the context of attenuating anxiety-like behaviors through ZL006 treatment, we observe a reduction in closed head injury-induced astrocyte engulfment, which may correlate with the observed decrease in dendritic spine density of medial prefrontal cortex glutamatergic neurons.

Microbiome Metabolomic Analysis of the Anxiolytic Effect of Baihe Dihuang Decoction in a Rat Model of Chronic Restraint Stress.

Purpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics. Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters. Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment. Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

BACKGROUND: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aß1-42). METHODS: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. RESULTS: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. CONCLUSIONS: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aß through modulation of oxidative-antioxidant status.

[Asthenia in young patients and possibilities for its correction]. / Asteniya u molodykh patsientov i vozmozhnosti ee korrektsii.

OBJECTIVE: To investigate the effect of using the drug Brainmax on various manifestations of asthenic syndrome. MATERIAL AND METHODS: 30 patients, average age 29 years (20-44 years) took part in the study. The duration of treatment was 15 days. Subjective indicators on the asthenic state scale, hospital anxiety and depression scale, daytime sleepiness scale, as well as objective indicators of the corrective test were analysed. RESULTS: It was found that after treating patients with Brainmax, the severity of asthenic syndrome, anxiety, and depression significantly decreased, the quality of sleep increased, and the results of the correction test improved. CONCLUSION: The drug Brainmax can be recommended for the correction of asthenic syndrome in patients with functional diseases of the nervous system.

Impact of chronic lithium treatment on brain oxidative stress and anxiety-like behaviors in rats: Dose-dependent effects.

Lithium (Li) is a mood-stabilizing drug. Although one of the potential mechanisms underlying the neuroprotective effects of lithium is related to its antioxidative effect, its mechanisms of action are not fully understood. Herein we aimed to investigate the impact of varied dosages of long-term lithium therapy on oxidative stress parameters in the brains of healthy rats, and on anxiety-like behaviors, and whether any changes in behavior can be attributed to modifications in oxidative stress levels within the brain. Thirty-two adult Wistar albino male rats were randomly assigned to four treatment groups. While the control (C) group was fed with a standard diet, low Li (1.4 g/kg/diet), moderate Li (1.8 g/kg/diet), and high Li (2.2 g/kg/diet) groups were fed with lithium bicarbonate (Li2CO3) for 30 days. Malondialdehyde increased, while superoxide dismutase and catalase levels decreased in the brains of the high Li group animals. In addition, anxiety-like behaviors of animals increased in the high Li group considering fewer entries to and less time spent in the open arms of the elevated plus maze test. Our findings underscore the potential adverse effects of prolonged lithium treatment, especially at doses approaching the upper therapeutic range. The induction of toxicity, manifested through heightened oxidative stress, appears to be a key mechanism contributing to the observed increase in anxiety-like behaviors. Consequently, caution is warranted when considering extended lithium therapy at higher doses, emphasizing the need for further research to delineate the precise mechanisms underlying these effects and to inform safer therapeutic practices.

Anxiolytic effects of Enterococcus faecalis 2001 on a mouse model of colitis.

Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the Enterococcus faecalis 2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and p-glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased N-methyl-D-aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII/CREB/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII/CREB/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.

Management of physical and psychological trauma resulting from motor vehicle crashes in Australian general practice: a mixed-methods approach.

BACKGROUND: In Australia, motor vehicle crashes (MVC)-related health data are available from insurance claims and hospitals but not from primary care settings. This study aimed to identify the frequency of MVC-related consultations in Australian general practices, explore the pharmacological management of health conditions related to those crashes, and investigate general practitioners' (GPs) perceived barriers and enablers in managing these patients. METHODS: Mixed-methods study. The quantitative component explored annual MVC-related consultation rates over seven years, the frequency of chronic pain, depression, anxiety or sleep issues after MVC, and management with opioids, antidepressants, anxiolytics or sedatives in a sample of 1,438,864 patients aged 16 + years attending 402 Australian general practices (MedicineInsight). Subsequently, we used content analysis of 81 GPs' qualitative responses to an online survey that included some of our quantitative findings to explore their experiences and attitudes to managing patients after MVC. RESULTS: MVC-related consultation rates remained stable between 2012 and 2018 at around 9.0 per 10,000 consultations. In 2017/2018 compared to their peers, those experiencing a MVC had a higher frequency of chronic pain (48% vs. 26%), depression/anxiety (20% vs. 13%) and sleep issues (7% vs. 4%). In general, medications were prescribed more after MVC. Opioid prescribing was much higher among patients after MVC than their peers, whether they consulted for chronic pain (23.8% 95%CI 21.6;26.0 vs. 15.2%, 95%CI 14.5;15.8 in 2017/2018, respectively) or not (15.8%, 95%CI 13.9;17.6 vs. 6.7%, 95% CI 6.4;7.0 in 2017/2018). Qualitative analyses identified a lack of guidelines, local referral pathways and decision frameworks as critical barriers for GPs to manage patients after MVC. GPs also expressed interest in having better access to management tools for specific MVC-related consequences (e.g., whiplash/seatbelt injuries, acute/chronic pain management, mental health issues). CONCLUSION: Chronic pain, mental health issues and the prescription of opioids were more frequent among patients experiencing MVC. This reinforces the relevance of appropriate management to limit the physical and psychological impact of MVC. GPs identified a lack of available resources (e.g. education, checklists and management support tools) for managing MVC-related consequences, and the need for local referral pathways and specific guidelines to escalate treatments.

Jnk1 and downstream signalling hubs regulate anxiety-like behaviours in a zebrafish larvae phenotypic screen.

Current treatments for anxiety and depression show limited efficacy in many patients, indicating the need for further research into the underlying mechanisms. JNK1 has been shown to regulate anxiety- and depressive-like behaviours in mice, however the effectors downstream of JNK1 are not known. Here we compare the phosphoproteomes from wild-type and Jnk1-/- mouse brains and identify JNK1-regulated signalling hubs. We next employ a zebrafish (Danio rerio) larvae behavioural assay to identify an antidepressant- and anxiolytic-like (AA) phenotype based on 2759 measured stereotypic responses to clinically proven antidepressant and anxiolytic (AA) drugs. Employing machine learning, we classify an AA phenotype from extracted features measured during and after a startle battery in fish exposed to AA drugs. Using this classifier, we demonstrate that structurally independent JNK inhibitors replicate the AA phenotype with high accuracy, consistent with findings in mice. Furthermore, pharmacological targeting of JNK1-regulated signalling hubs identifies AKT, GSK-3, 14-3-3 ζ/ε and PKCε as downstream hubs that phenocopy clinically proven AA drugs. This study identifies AKT and related signalling molecules as mediators of JNK1-regulated antidepressant- and anxiolytic-like behaviours. Moreover, the assay shows promise for early phase screening of compounds with anti-stress-axis properties and for mode of action analysis.

Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.

BACKGROUND: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. METHODS: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. RESULTS: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. CONCLUSIONS: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.

Indulging Curiosity: Preliminary Evidence of an Anxiolytic-like Effect of Castor Oil and Ricinoleic Acid.

In the process of validating the elevated zero maze, a common test of anxiety-like behavior, in our laboratory, we demonstrated an anxiolytic-like effect of castor oil and its primary component, ricinoleic acid. We tested the effects of vehicle and chlordiazepoxide in male mice in the elevated zero maze following a 30-min pretreatment time. Chlordiazepoxide is a United States Food and Drug Administration-approved drug that was previously shown to exert anxiolytic-like effects in both the elevated zero maze and elevated plus maze. Chlordiazepoxide was administered at doses of 5 or 10 mg/kg. We used 5% polyoxyl 35 castor oil (Kolliphor® EL) and saline as treatment vehicles and found that the effect of chlordiazepoxide on open zone occupancy and open zone entries was blunted when 5% Kolliphor was used as the vehicle. These tests demonstrated that chlordiazepoxide increased open zone occupancy and entries in the elevated zero maze more effectively when saline was used as the treatment vehicle and that Kolliphor dampened the anxiolytic-like effect of chlordiazepoxide when it was used as the treatment vehicle. Notably, 5% Kolliphor alone slightly increased baseline open zone occupancy and entries. Given that Kolliphor is a derivative of castor oil, we next tested the effect of 5% castor oil and 5% ricinoleic acid, which is a major component of castor oil. We found that both castor oil and ricinoleic acid increased open zone occupancy but not entries compared with saline. Altogether, our findings demonstrate that Kolliphor, castor oil, and ricinoleic acid may exert anxiolytic-like effects in male mice in the elevated zero maze. This potential anxiolytic-like effect of castor oil is consistent with its well-established beneficial effects, including anti-inflammatory, antioxidant, antifungal, and pain-relieving properties.

Dexmedetomidine attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18-23 g) were randomly divided into a control group (control, N = 10), dexmedetomidine group (Dex, N = 10), AS with normal saline group (AS + NS, N = 10) and AS with dexmedetomidine group (AS + Dex, N = 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia (A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Neuro-protective effect of pre-treatment with Sorghum bicolor and vitamin C on tramadol induced brain oxidative stress and anxiety-like behaviour in male albino rats.

The study focused on the neuroprotective role of Sorghum bicolor and vitamin C in the amelioration of oxidative stress and anxiety-like behavoiur induced by tramadol in male albino rats. The study design involved 7 groups and a control group with 5 male albino rats in each group. Tramadol (40 mg/kg) treatment was administered for 21 days. Tramadol 40mg/kg was administered in all groups. Pretreatment with varying doses of Sorghum bicolor and Vitamin C was done in three of the groups. Behavioral assessment of anxiety and locomotors actions of the groups were compared using Elevated Plus Maze (EPM) and Open Field Test (OFT). In conclusion, Sorghum bicolor and Vitamin C tramadol ameliorated oxidative stress and anxiety-like behaviour induced by tramadol. Pretreatment with Sorghum bicolor or vitamin C (100mg) can also reduced anxiogenic responses in male albino rats that are induced by chronic tramadol use.

Effect of intramuscular diazepam infusion on herpes zoster-related pain in older patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study evaluated the effectiveness, psychological effects, and sleep quality using intramuscular diazepam infusion compared with placebo in patients with herpes zoster (HZ)-related pain. METHODS: The patients were randomized to either the diazepam or control group. The diazepam group received an intramuscular injection of diazepam for 3 consecutive days, while the control group received an intramuscular injection of 0.9% normal saline. The primary outcome was pain relief on posttreatment day 4, as measured using the Visual Analog Scale (VAS). Moreover, anxiety and depression were evaluated using the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9), respectively. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: In total, 78 patients were enrolled in the trial. The mean differences in VAS scores between the two groups were 0.62 (P = 0.049) on posttreatment day 3 and 0.66 (P = 0.037) on posttreatment day 4. The effective rates of pain management in the diazepam group ranged from 10.26 to 66.67%, which were higher than those in the control group on posttreatment days 3 and 4 (P < 0.05). The mean difference in PSQI scores between the diazepam and control groups was 1.36 (P = 0.034) on posttreatment day 7. No differences were found in the incidence of analgesia-adverse 1reactions between the diazepam and placebo groups. CONCLUSIONS: The intramuscular injection of diazepam for 3 consecutive days provides effective pain management and improves the quality of life. Our study suggests that diazepam is more effective than the placebo in patients with HZ-related pain. TRIAL REGISTRATION: The study was prospectively registered at https://www.isrctn.com/trialist(Registration date: 24/01/2018; Trial ID: ISRCTN12682696).

The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.

BACKGROUND: In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD. METHODOLOGY/PRINCIPAL FINDINGS: In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells. CONCLUSION/SIGNIFICANCE: We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders.

Mindfulness in Facilitating Pelvic Floor Botulinum Toxin Injection in Women with Chronic Pelvic Pain.

Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to increase the tolerability of office-based pelvic floor BoNT injections in women with CPP. Women enrolled in a clinical trial of BoNT for endometriosis-associated CPP were offered a brief, guided mindfulness session before and/or after transvaginal injection. Anxiety, pain, and dysphoria were rated on a 0-10 numerical rating scale (NRS) before and after each mindfulness session. Eight women underwent mindfulness sessions. Five participants had a session before and two after the transvaginal injection. One participant had two sessions: one before and one after separate injections. All six women completing a session prior to injection had at least moderate anxiety, which lessened after the mindfulness session (median NRS change: -3.3/10). All three women reporting injection-associated pain experienced less intense pain following the post-injection session (median NRS change: -3/10). Three women experiencing dysphoria improved after the session (median NRS change: -3/10). A brief, guided mindfulness session may lessen acute pain, anxiety, and dysphoria associated with office-based transvaginal BoNT injection.

Neuro-stimulating effect of Citri Reticulata Pericarpium Viride essential oil through regulating Glu/NMDAR on olfactory bulb to improve anxiety-like behavior.

ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. AIM OF THE STUDY: The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. MATERIALS AND METHODS: This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. RESULTS: The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. CONCLUSIONS: The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

Pharmacotherapy of Chronic Neuropsychiatric Conditions During Pregnancy.

Many pregnant persons will experience neuropsychiatric conditions during pregnancy, including migraine, attention deficit disorder, depression, and anxiety. Treatment of each of these conditions requires shared decision-making among the individual, family, and health care team. Although medications may include risk, the benefits often outweigh the potential fetal risks. In this article, we review pharmacologic treatment options for each of these conditions and appropriate use in pregnancy to maintain the stability of conditions and to optimize maternal and fetal outcomes.

Evaluation of New Approaches to Depression Treatment Using an Animal Model of Pharmacoresistant Depression.

Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group (p < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine (p < 0.05 central zone; p ≤ 0.05 periphery zone) and SMe1EC2M3 (p < 0.05 central zone; p < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST (p < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group (p < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group (p < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.

Early evidence of beneficial and protective effects of Protectin DX treatment on behavior responses and type-1 diabetes mellitus related-parameters: A non-clinical approach.

Protectin DX (PDX), a specialized pro-resolving lipid mediator, presents potential therapeutic applications across various medical conditions due to its anti-inflammatory and antioxidant properties. Since type-1 diabetes mellitus (T1DM) is a disease with an inflammatory and oxidative profile, exploring the use of PDX in addressing T1DM and its associated comorbidities, including diabetic neuropathic pain, depression, and anxiety becomes urgent. Thus, in the current study, after 2 weeks of T1DM induction with streptozotocin (60 mg/kg) in Wistar rats, PDX (1, 3, and 10 ng/animal; i.p. injection of 200 µl/animal) was administered specifically on days 14, 15, 18, 21, 24, and 27 after T1DM induction. We investigated the PDX's effectiveness in alleviating neuropathic pain (mechanical allodynia; experiment 1), anxiety-like and depressive-like behaviors (experiment 2). Also, we studied whether the PDX treatment would induce antioxidant effects in the blood plasma, hippocampus, and prefrontal cortex (experiment 3), brain areas involved in the modulation of emotions. For evaluating mechanical allodynia, animals were repeatedly submitted to the Von Frey test; while for studying anxiety-like responses, animals were submitted to the elevated plus maze (day 26) and open field (day 28) tests. To analyze depressive-like behaviors, the animals were tested in the modified forced swimming test (day 28) immediately after the open field test. Our data demonstrated that PDX consistently increased the mechanical threshold throughout the study at the two highest doses, indicative of antinociceptive effect. Concerning depressive-like and anxiety-like behavior, all PDX doses effectively prevented these behaviors when compared to vehicle-treated T1DM rats. The PDX treatment significantly protected against the increased oxidative stress parameters in blood plasma and in hippocampus and prefrontal cortex. Interestingly, treated animals presented improvement on diabetes-related parameters by promoting weight gain and reducing hyperglycemia in T1DM rats. These findings suggest that PDX improved diabetic neuropathic pain, and induced antidepressant-like and anxiolytic-like effects, in addition to improving parameters related to the diabetic condition. It is worth noting that PDX also presented a protective action demonstrated by its antioxidant effects. To conclude, our findings suggest PDX treatment may be a promising candidate for improving the diabetic condition per se along with highly disabling comorbidities such as diabetic neuropathic pain and emotional disturbances associated with T1DM.