Anxiolytic Effects Research Articles

Cannabidiol for treatment of Irritability and Aggressive Behavior in Children and Adolescents with ASD: Background and Methods of the CAnnabidiol Study in Children with Autism Spectrum DisordEr (CASCADE) Study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder commonly associated with behavioral challenges. There are few evidence based pharmacological interventions available for the treatment of behavioral symptoms associated with ASD. Cannabidiol (CBD), the non-psychoactive component of cannabis, has potential neuroprotective, antiepileptic, anxiolytic, and antipsychotic effects and may be useful in treating the behavioral symptoms of ASD. We describe the research methods of a 27-week double-blind placebo-controlled cross-over trial of cannabidiol for the treatment of irritability and aggression associated with ASD, utilizing the irritability subscale of the Aberrant Behavior Checklist-2nd edition (ABC-2) as the primary outcome measure. Adverse effects and safety monitoring protocols are included. Several secondary and exploratory outcomes measures also include anxiety, communication, repetitive behaviors, attention, hyperactivity, autism family experience, and telehealth functional behavior assessment. There is a significant need for clinical research exploring alternative medications for the treatment of behavioral symptoms of ASD. Cannabidiol (CBD) is being studied for the management of irritability, aggression, and other problem behaviors associated with ASD.

Perioperative dexmedetomidine-induced delirium in a patient with schizophrenia: a case report

BackgroundDexmedetomidine is a selective α2 receptor agonist with sedative, analgesic, anxiolytic, and anti-sympathetic effects. Dexmedetomidine is widely used for various surgical procedures performed under general anaesthesia and sedation in the intensive care unit. Dexmedetomidine was known to relieve or improve the symptoms of delirium. Schizophrenia is a common psychiatric disease, and the number of surgical patients with schizophrenia is increasing gradually. Dexmedetomidine-induced delirium in patients with schizophrenia is a particular case.Case presentationThis patient was a 75-year-old woman (height: 156 cm; weight: 60 kg) with a 5-year history of schizophrenia. Her schizophrenia was well controlled with medications. She was scheduled for open reduction and internal fixation for a patellar fracture. Spinal anaesthesia was administered for surgery, and dexmedetomidine was administered intravenously to maintain sedation. The patient became delirious half an hour after the surgery began. The intravenous infusion of dexmedetomidine was discontinued immediately, intravenous propofol was subsequently administered, and the patient stopped experiencing dysphoria and fell asleep. After surgery, the patient stopped using propofol and recovered smoothly. She was transferred back to the general ward and was discharged from the hospital without any abnormal conditions on the 9th day after surgery.ConclusionsTo the best of our knowledge, this is the first report of a patient with schizophrenia who developed delirium during the infusion of a normal dose of dexmedetomidine without an intravenous injection of any other sedative. The exact mechanism causing dexmedetomidine-induced delirium remains unclear, and this adverse reaction is rare and easy to ignore. Clinicians and pharmacists should be vigilant in identifying this condition.

Astrocytes in the Ventral Hippocampus Bidirectionally Regulate Innate and Stress-Induced Anxiety-Like Behaviors in Male Mice.

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.

The effect of preoperative music therapy on perioperative anxiety and cognitive functions in adult patients in Erzincan, Turkey: a cohort study

Background & objective: Perioperative anxiety affects 25-80% of all surgical patients. It has a negative impact on postoperative recovery, potentially increasing morbidity and mortality. The anxiolytic effects of music therapy are well recognized, but its cognitive implications are unknown. We examined the effects of 440 Hz and 432 Hz music therapy on pre-operative anxiety and cognitive functions in patients scheduled for surgery. Methodology: The study took place in the operating room of our hospital. Following ethical committee approval, the study was launched. It was a prospective observational study comprising 66 ASA I, II, and III patients, between the ages of 18 and 65, scheduled to undergo surgery. They were divided into three groups: Control Group (CG), music therapy at 440 Hz (MG440), and music therapy at 432 Hz (MG432). Music therapy was administered to MG440 and MG432, but not to CG. Patients took the Montreal Cognitive Assessment (MoCA) and the Beck Anxiety Scale (BAS). MoCA and BAS were assessed before surgery, one hour and at 24 hours following surgery. Results: In both groups, preoperative music therapy significantly reduced anxiety (P < 0.001). Anxiety levels following surgery were comparable in all groups. Postoperative one-hour cognitive performance in music therapy groups was lower than in controls (P < 0.001), but increased and became significantly higher than in the control group at 24 h (P < 0.001). There was no substantial difference between the 440 Hz and 432 Hz groups. Conclusions: Preoperative music therapy reduced anxiety; it initially lowered postoperative cognitive performance; nevertheless, within 24 hours, therapy groups had enhanced cognitive skills when compared to controls. Ethical committee approval: (Protocol No. 2023-01/2, Date: May 1, 2023). Abbreviations: BAS - Beck Anxiety Scale; MoCA - Montreal Cognitive Assessment; Keywords: Music; Therapeutics; Anxiety; Cognition; Anesthesia, General Citation: Tas HG, Subası F, Hayme S, Akkus M, Kuyrukluyıldız U. The effect of preoperative music therapy on perioperative anxiety and cognitive functions in adult patients in Erzincan, Turkey: a cohort study. Anaesth. pain intensive care 2024;28(4):658−663; DOI: 10.35975/apic.v28i4.2508 Received: February 21, 2024; Reviewed: June 20, 2024; Accepted: June 20, 2024

Ameliorative Effect of Polypodium vulgare L. Rhizome on Anxiety and Depressive-Like Behaviors in Restraint-Subjected Mice: Involvement of Inflammatory, Oxidative and Apoptotic Pathways

Background: Developing drugs with higher efficacy and fewer side effects for psychological disorders has always been of interest. The rhizome of Polypodium vulgare L. (common polypody) has been used as a mood stabilizer in Persian medicine (PM). Objectives: The present study evaluates the anxiolytic and antidepressant effects of the hydroethanolic extract of common polypody rhizome (PEE) and the possible underlying mechanisms in mice subjected to chronic restraint stress (CRS). Methods: Sixty NMRI male mice were exposed to CRS and received either a vehicle, fluoxetine, or PEE (at doses of 250, 500, 1000, and 1500 mg/kg-1). The forced swim test (FST), tail suspension test (TST), open-field test (OFT), and elevated-plus maze (EPM) were conducted to evaluate depressive-like and anxiety-like behavior. Oxidative, inflammatory, and apoptotic markers, as well as brain-derived neurotrophic factor (BDNF), were measured in the prefrontal cortex (PFC) and hippocampus (HIP). Corticosterone levels were also assessed in serum samples. Results: Polypody rhizome increased the time spent in the central zone of the OFT, as well as the time spent and the number of entries into the open arms of the EPM, while it decreased the immobility time in the FST and TST. Administration of PEE caused a significant decline in serum levels of corticosterone, as well as tissue levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and malondialdehyde (MDA). Additionally, it increased superoxide dismutase (SOD) activity in the PFC and HIP. Polypody rhizome also significantly restored total antioxidant capacity (TAC), glutathione peroxidase (GPx) activity, and BDNF expression in the HIP. Moreover, Bcl-2 levels increased in the PFC, and Bax and caspase-3 expressions were downregulated in both regions with PEE administration. Conclusions: Polypody rhizome exerted anxiolytic and antidepressant effects in behavioral tests and reversed CRS-induced oxidative, inflammatory, and apoptotic alterations.

Elucidating the potential role of microorganisms in postmortem biotransformation: a comparison of clonazolam and its metabolite in postmortem and DUID cases.

Clonazolam is a designer triazolobenzodiazepine first synthesized in 1971 and is primarily used for its anxiolytic and sedative effects. It became a drug of misuse in 2012 and is known for its high potency and long duration of effect. Previous studies of nitrobenzodiazepines, such as nitrazepam, clonazepam, and flunitrazepam, as well as their metabolites, have demonstrated that bacterial species native to the gastrointestinal tract and active during postmortem (PM) decomposition are capable of affecting positivity and compound-to-metabolite ratios. Further studies have not been performed with clonazolam; however, it possesses the nitro functional group necessary for this biotransformation. To understand whether clonazolam may be similarly affected, PM cases (n = 288) and driving under the influence of drugs (DUID, n = 54) cases, positive for 8-aminoclonazolam reported by NMS Laboratories from 2020 to 2023, were selected for inclusion in this study. Concentrations of clonazolam and 8-aminoclonazolam were evaluated, and concurrent identification of parent drugs and their metabolites occurred less frequently in PM cases (n = 1, 0.30% of cases) than in DUID cases (n = 21, 38% of cases). The clonazolam concentration in one PM case was 13 ng/mL. In DUID cases, the median clonazolam concentration was 4.0 ng/mL and ranged from 2.0 to 10 ng/mL. 8-Aminoclonazolam had median concentrations of 13 and 19 ng/mL, with ranges 2.0-580 and 2.8-59 ng/mL for PM and DUID cases, respectively. Due to the ever-changing landscape of the designer benzodiazepine market, in vitro studies of PM microbial biotransformation of clonazolam are unavailable. The data reported herein provide valuable information in the absence of such studies and represent an alternative method of investigating this phenomenon as a potential cause of parent nitrobenzodiazepine to metabolite conversion.

The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions

Many experts have extensively studied the potential of exercise as a treatment option for psychiatric conditions, including depression and autism spectrum disorder (ASD). Despite their core symptoms, these conditions exhibits comparable component traits, an anxiety. In this study, we explored the effect of exercise on behavioral abnormalities in psychiatric conditions, focusing on its intensity and emotional resilience. Shank3B knockout (KOSED) mice displaying self-injurious repetitive behavior and C57BL/6J mice, susceptible to stress as ASD and depression model, respectively, were subjected to moderate-intensity exercise (ME) for 2 weeks. ME mitigated the core symptoms (excessive grooming traits and behavioral despair) but did not exert a significant anxiolytic effect. Notably, exercise intensity has emerged as a critical determinant of its efficacy, as evidenced by a lower ventilation threshold and anxiolytic effect mediated by low-intensity exercise. The findings substantiate the notion that exercise is promising as a disease-modifying treatment, but intensity matters for emotional resilience.Graphical

New insights about the antidepressant-like effects of riparin A in a chronic murine model of depression.

Riparin A is a synthetic form of natural riparins. Acute scale studies that take into consideration the structure-activity relationship have shown preliminary evidence of antidepressant and anxiolytic effects of riparin A, similar to that already known for other riparins. However, for better pharmacological characterization of this new compound, further studies are required. The aim of this work was to evaluate the effect of chronic treatment with riparin A (10 mg/kg; intraperitoneally) on depressive-like behavior in the forced swimming test and tail suspension test, as well as the reduction of anhedonia in the sucrose preference test, and on anxiety-like behavior in the open field and elevated plus maze apparatus, triggered in rats previously subjected to unpredictable chronic mild stress by 4 weeks. In addition, a pentobarbital-induced sleep time test was also used. Riparin A reduced the duration of immobility in both the forced swimming test and tail suspension test, as well as attenuated the anhedonia in the sucrose preference test. Furthermore, riparin A appears to produce anxiolytic effects in rats exposed to an open field and elevated plus maze, while increasing the alertness/vigilance in rats submitted to pentobarbital-induced sleep time test, without altering their locomotor integrity. Our results suggest that chronic riparin A appears to be a potential pharmacological target for new studies on the control of depression- and anxiety-like behaviors in stressed rats.

Evidence of HARKing in mouse behavioural tests of anxiety.

Over the last decades, behavioural tests in animals, especially rodents, have been a standard screening method to determine the mechanisms of action and efficacy of psychopharmacological compounds. Yet, recently the reproducibility of some of these tests has been questioned. Based on a systematic review of the sensitivity of mouse behavioural tests to anxiolytic drugs, we analysed behavioural outcomes extracted from 206 studies testing the effect of diazepam in either the open-field test or the hole-board test. Surprisingly, we found that both the rationale given for using the test, whether to detect anxiolytic or sedative effects, and the predicted effect of diazepam, anxiolytic or sedative, strongly depended on the reported test results. The most likely explanation for such strong dependency is post hoc reasoning, also called hypothesizing after the results are known (HARKing). HARKing can invalidate study outcomes and hampers evidence synthesis by inflating effect sizes. It may also lead researchers into blind alleys, and waste animals, time and resources for inconclusive research.

Evaluating the Cognitive Impact of Anxiolytics on Elderly Patients: A prospective observational study.

Background: The cognitive effects of anxiolytics in older adults are an important domain to research given the high rates of anxiety disorders and these medications commonly prescribed. Benzodiazepines, and some of the newer non-benzo" sedative anxiolytic agents have been associated with cognitive effects as a potential side effect. This study is going to be conducted in Lady Reading Hospital (LRH) Peshawar; thus the data will reflect upon population served by this particular hospital. Objectives: To assess the cognitive impact of anxiolytic medication in geriatric patients, specifically on short-term memory (STM), attention and executive functions. Design: A observational study. Place and Duration of Study: Department of Pharmacy, Lady Reading Hospital-Peshawar starting from January 05th 2021 to July 05th ,2022. Methods: This was an observational study conducted on 150 elderly patients at Lady Reading Hospital through non probability sampling, comparing cognitive domain of functioning between 75 users and rest controls. Cognitive function was evaluated by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment before and after the medication. Results - This section will describe the cognitive score changes in relation to anxiolytic use. One-way ANOVA will be utilized to examine the differences in cognitive outcomes according drug type, dosage and duration of use. Conclusions: The use of anxiolytics in elderly patients is associated with deterioration cognitive function, which was confirmed by a decrease MMSE and MoCA scores during the course of treatment. The potential cognitive side effects when prescribing anxiolytics to the elderly requires a nuanced approach by healthcare providers. Keywords: Anxiolytics; older adult patients; cognitive performance, MMSE/MoCA.

WAY-208466, a 5-HT6 receptor agonist, increases food motivation in primates: A behavioural and PET imaging study opening perspectives in eating disorders

The 5-HT6 receptor (5-HT6R) is highly expressed in the anterior striatum, a region involved in food-intake and anxiety-related behaviours that shows abnormal activity in anorexia nervosa (AN) patients. Indeed, 5-HT6R antagonists decrease food motivation across species. Rodent studies have shown the acute anxiolytic properties of WAY-208466, a selective 5-HT6R agonist. Thus, we hypothesized that this agent could increase food motivation and decrease anxiety-related behaviours by impacting cortico-striatal circuits. We administered acute (0.1 mg/kg) and subchronic (0.03 and 0.1 mg/kg) intramuscular injections to four macaques performing a food-choice task and expressing spontaneous behaviours. We used PET imaging with the [18F]2FNQ1P specific tracer to determine 5-HT6R occupancy in several regions that could be linked with the induced behavioural changes. Acute and subchronic activation of 5-HT6R transmission led to a reversible increase in food motivation. WAY-208466 also decreased anxiety-like behaviours when given acutely but not subchronically. However, in the subchronic protocol, the higher dose led to increased activity characterized by movements and object-related behaviour expression. PET imaging revealed that these behavioural changes could be sustained by cortico-striatal circuits involved in food intake. These findings demonstrate that this 5-HT6R agonist subchronic treatment successfully increases food motivation but does not fully achieve the expected anxiolytic effect in monkeys. It suggests that targeting 5-HT6Rs may be a promising approach for treating the restrictive subtype of AN, which, unlike anxiety, has not been shown to benefit from treatment with selective serotonin reuptake inhibitors.

Peribulbar Block for Cataract Surgery in Patient with Nystagmus and Chronic Kidney Disease

Background: Management of presenile cataracts with nystagmus and chronic kidney (CKD) disease is a separate problem in anesthetic procedures. The risk of anesthesia in patients with chronic kidney disease is accumulation of nephrotoxic metabolites, unstable hemodynamic during intraoperative, and fluid overload.Case: A 43-year-old man with a diagnosis of immature presenile cataract with nystagmus and comorbid CKD was planned for phacoemulsification and intraocular lens. The anesthetic technique used was regional anesthesia with peribulbar block. Site injections in the inferotemporal and medial canthus with local anesthetic drugs levobupivacaine 0.5% 5 ml and lidocaine 2% 3 ml.Discussion: Combination of peribulbar block and mild sedation provides effective analgesic and anxiolytic effects. Peribulbar blocks in nystagmus besides sensory blocks can also block motoric function so that the position of the eyeball is in center.Conclusion: The peribulbar blockade anesthetic technique can be considered as an alternative safe anesthetic technique for cataract surgery with nystagmus and CKD.

A Systematic Review on Sedative and Hypnotics

Abstract: Sedative and hypnotic drugs are central nervous system depressants primarily used to induce calmness, reduce anxiety, and promote sleep. These medications include benzodiazepines, barbiturates, and various non-benzodiazepine sleep aids, each varying in their mechanism of action, efficacy, and safety profiles. Benzodiazepines, such as diazepam and alprazolam, enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in sedative, anxiolytic, muscle relaxant, and anticonvulsant effects. They are commonly prescribed for anxiety disorders, insomnia, seizures, and muscle spasms. However, their use is associated with risks of tolerance, dependence, and withdrawal symptoms. Barbiturates, such as phenobarbital, were once widely used for their sedative and hypnotic properties but have largely been replaced by benzodiazepines and other safer alternatives due to their higher risk of overdose and dependence. Barbiturates enhance GABAergic transmission but also directly activate GABA receptors, leading to more profound central nervous system depression. Non-benzodiazepine sleep aids, including drugs like zolpidem, eszopiclone, and zaleplon, act on the benzodiazepine receptor site but have a different chemical structure. These drugs are often preferred for short-term treatment of insomnia due to their relatively lower risk of dependence and adverse effects compared to benzodiazepines.

Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the vlPAG and the Analgesic and Anxiolytic Effects of EA.

Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.Significance Statement Neuropathic pain is clinically accompanied by anxiety. Both glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) and electroacupuncture (EA) have demonstrated analgesic properties. However, the efficacy of these interventions in addressing neuropathic pain and its concomitant anxiety has yet to be fully elucidated. In a mice model of spared nerve injury (SNI), we observed a decreased excitability of vlPAG CamkIIα neurons. Remarkably, EA treatment significantly enhanced the excitability of these neurons. Further, chemogenetic activation of vlPAGCamkIIα+ neurons not only resulted in analgesia but also mitigated anxiety-like behaviors in SNI mice, mirroring the effects observed with EA treatment. Conversely, inhibition of vlPAGCamkIIα+ neurons activity in naive mice reduced pain thresholds and induced anxiety-like behavior, while also negating the beneficial effects of EA. These findings provide novel insights into the mechanistic interplay between chronic neuropathic pain and anxiety, highlighting the therapeutic potential of targeting vlPAG glutamatergic neurons in these conditions.

Potential role of remimazolam in alleviating bone cancer pain in mice via modulation of translocator protein in spinal astrocytes

Bone cancer pain (BCP) is a complex clinical challenge, with current treatments often falling short of providing adequate relief. Remimazolam, a benzodiazepine receptor agonist recognized for its anxiolytic effects, has emerged as a potential agent in managing BCP. This study explores the analgesic properties of remimazolam and its interaction with the translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, in spinal astrocytes. In the context of BCP, previous research has indicated that TSPO expression in spinal astrocytes may serve a protective regulatory function in neuropathic pain models. Building on this, the BCP mice received various doses of remimazolam on the 15th day post-inoculation, and pain behavior was assessed over time. The results showed that BCP induced an upregulation of TSPO and astrocyte activation in the spinal dorsal horn, alongside increased extracellular signal-regulated kinase (ERK) signaling and inflammatory cytokine expression. Remimazolam administration resulted in a dose-dependent reduction of pain behaviors, which corresponded with a decrease in both ERK pathway activation and inflammatory factor expression. This suggests that remimazolam's analgesic effects are mediated through its action as a TSPO agonist, leading to the attenuation of neuroinflammation and pain signaling pathways. Importantly, the analgesic effects of remimazolam were reversed by the TSPO antagonist PK11195, underscoring the pivotal role of TSPO in the drug's mechanism of action. This reversal also reinstated the heightened levels of ERK activity and inflammatory mediators, further confirming the involvement of TSPO in the modulation of these pain-related processes. These findings open new avenues for the therapeutic management of bone cancer pain, positioning remimazolam as a promising candidate for further investigation and development.

Antidepressant activity of tricin-7-O-glucoside and anxiolytic-like effect of harmane from Passiflora coriacea Juss. On mice

Ethnopharmacological relevancePassiflora coriacea Juss., a medicinal plant in the family Passifloraceae, is widely used to treat anxiety and depression in Mexican folk medicine. However, its chemical profile and biological activity have not been characterized. Aim of the studyThe aim of the study was to determine the antidepressant activity, anxiolytic effect, and chemical profile of Passiflora coriacea. Materials and methodsAn organic fraction (PcEA) from a hydroalcoholic extract of the aerial parts of P. coriacea was obtained, followed by a chemical analysis and separation, yielding six fractions (PcEA, T1, T2, T1.1, T2.1, and T2.2). Male ICR mice were used to determine the antidepressant activity of selected treatments (PcEA, T1, T2, and T1.1) based on a forced swim test (FST). The anxiolytic-like effects of various treatments (PcEA, T1, T2, T2.1, and T2.2) were determined using the elevated plus maze (EPM) test. ResultsThe organic fraction of P. coriacea decreased anxiety-like behaviors in mice and increased the time of mobility in the FST. After chemical separation, two compounds were isolated from the species with antidepressant activity and anxiolytic-like effects, T1.1 (tricin 7-O-glucoside) and T2.2 (harmane), respectively. ConclusionsCompounds isolated from P. coriacea exerted anxiolytic and antidepressant effects in mice based on the EPM and FST. The flavonoid tricin-7-O-glucoside and the alkaloid harmane contributed to these biological activities.

The Study of TRPV1 Channels of the Central Nervous System and Their Effect on Anxiety in ICR Mice.

The TRPV1 channel is actively involved in various neuronal processes and is found in various structures of the nervous system, including peripheral and central neurons, sensory ganglia, spinal cord, and various parts of the brain. Due to its ability to respond to various stimuli, TRPV1 can have a significant impact on the body's responses to stress. Studies indicate the involvement of TRPV1 in the regulation of anxiety behavior. Suppression of TRPV1 activity leads to a decrease in the level of anxiety in animals, which indicates the importance of this channel in psychoemotional regulation. A promising compound for inhibiting this channel is the APHC3 peptide, which is a selective receptor antagonist. The results obtained this study show that this peptide has a pronounced anxiolytic effect, reducing the level of anxiety in the studied animals.

Apocynin Prevents Cigarette Smoke-Induced Anxiety-Like Behavior and Preserves Microglial Profiles in Male Mice.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and is primarily caused by cigarette smoking (CS). Neurocognitive comorbidities such as anxiety and cognitive impairments are common among people with COPD. CS-induced lung inflammation and oxidative stress may "spill-over" into the systemic circulation, driving the onset of these comorbidities. We investigated whether a prophylactic treatment with the NADPH Oxidase 2 (NOX2) inhibitor, apocynin, could prevent CS-induced neurocognitive impairments. Adult male BALB/c mice were exposed to CS (9 cigarettes/day, 5 days/week) or room air (sham) for 8 weeks with co-administration of apocynin (5 mg/kg, intraperitoneal injection once daily) or vehicle (0.01% DMSO in saline). Following 7 weeks of CS exposure, mice underwent behavioral testing to assess recognition and spatial memory (novel object recognition and Y maze, respectively) and anxiety-like behaviors (open field and elevated plus maze). Mice were then euthanized, and blood, lungs, and brains were collected. Apocynin partially improved CS-induced lung neutrophilia and reversed systemic inflammation (C-reactive protein) and oxidative stress (malondialdehyde). Apocynin exerted an anxiolytic effect in CS-exposed mice, which was associated with restored microglial profiles within the amygdala and hippocampus. Thus, targeting oxidative stress using apocynin can alleviate anxiety-like behaviors and could represent a novel strategy for managing COPD-related anxiety disorders.

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster).

The social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (Microtus ochrogaster). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we assessed the functional significance of OXTR in stress-induced social avoidance and the response of the MAPK signaling pathway in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) of female prairie voles. In experiment 1, Sexually naïve adult female prairie voles were defeated for three consecutive days and tested a week after for social preference/avoidance (SPA) test. Control subjects were similarly handled without defeat conditioning. In experiment 2, sexually and stress naïve adult female prairie voles were bilaterally injected into the NAc, ACC, or the BLA with a CRISPR/Cas9 virus targeting the Oxtr coding sequence to induce OXTR knockdown. Two weeks post-surgery, subjects were tested for SPA behavior. Viral control groups were similarly handled but injected with a control virus. A subgroup of animals from each condition in both experiments were similarly treated and euthanized without being tested for SPA behavior. Brains were harvested for OXTR autoradiography, western blot analysis of MAPK proteins and quantification of local oxytocin content in the NAc, BLA, ACC, and PVN through ELISA. Social defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to the SPA test. Additionally, OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown in these regions was associated with less availability of oxytocin in the PVN. Dysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could, therefore, play an important role in the etiology of SAD in women.

Astounding the anxiolytic and eudemonic potential of certain fruits

Anxiety is a state of mind with some fear that affects physical health by disrupting neurotransmission and hormonal control. Both diet (inadequate and unhealthy dietary patterns) and environment (social and financial factors) trigger its progression; therefore, diet is considered to have a significant involvement in its prevention or adjunct therapy. A unique nutrient profile and bioactive ingredients are seen in fruits to provide health outcomes beyond nutritive properties. The relaxing potential of such fruits is attributed to the functional nature and therapeutic ingredients i.e., catecholamines, myricetin, quercetin, betalains, etc. that enhance the efficiency of hormones, neurotransmitters, and metabolic pathways. This review presented certain fruits having positive associations with mental health and anxiety amelioration. Various types of research evidenced the anxiolytic effect of certain fruits through clinical trials. Among them, berries, opuntia, and black pepper also have shown anxiety-relieving effects in clinical studies by restoring antioxidant enzymes, hormonal modulations, and managing neurotransmitters. Citrus species are loaded with flavonoids which are involved in the expression of GABA (Gamma-Amino Butyric Acid) to calm the nervous system. Some other fruits also potentiate memory and cognition when taken in ample amounts owing to their secondary metabolites. Thus, the incorporation of such fruits into a regular diet has been found to have a significant impact on mental well-being and brain health.