Anxiolytic Efficacy Research Articles

Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways.

Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open-field (square cross, grooming, and rearing), swing, dark-light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND-10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose-dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (-7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (-6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug-likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways.

Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice

Alcohol use disorder (AUD) is frequently comorbid with anxiety disorders, yet whether alcohol abuse precedes or follows the expression of anxiety remains unclear. Rodents offer control over the first drink, an advantage when testing the causal link between anxiety and AUD. Here, we utilized a risk-avoidance task to determine anxiety-like behaviors before and after alcohol exposure. We found that alcohol’s anxiolytic efficacy varied among inbred mice and mice with high risk-avoidance showed heightened alcohol relief. While dopamine D1 receptors in the striatum are required for alcohol’s relief, their levels alone were not correlated with relief. Rather, the ratio between striatal D1 and D2 receptors was a determinant factor for risk-avoidance and alcohol relief. We show that increasing striatal D1 to D2 receptor ratio was sufficient to promote risk-avoidance and enhance alcohol relief, even at initial exposure. Mice with high D1 to D2 receptor ratio were more prone to continue drinking despite adverse effects, a hallmark of AUD. These findings suggest that an anxiety phenotype may be a predisposing factor for AUD.

Nonsedating anxiolytics.

Anxiety disorders are the most prevalent psychiatric pathology with substantial cost to society, but the existing treatments are often inadequate. This has rekindled the interest in the GABAA-receptor (GABAAR) positive allosteric modulator (PAM) compounds, which have a long history in treatment of anxiety beginning with diazepam, chlordiazepoxide, and alprazolam. While the GABAAR PAMs possess remarkable anxiolytic efficacy, they have fallen out of favor due to a host of adverse effects including sedation, motor impairment, addictive potential and tolerance development. A substantial effort was thus devoted to the design of GABAAR PAMs as anxiolytics with reduced sedative liabilities. Several non-benzodiazepine (BZD) GABAAPAMs progressed to clinical trials (bretazenil, abecarnil, alpidem, and ocinaplon) with alpidem obtaining regulatory approval as anxiolytic, but later withdrawn from market due to hepatotoxicity. Advances in molecular biology gave birth to a host of subtype selective GABAAR-PAMs which suffered from signs of sedation and motor impairment and only three compounds progressed to proof-of-concept studies (TPA-023, AZD7325 and PF-06372865). TPA-023 was terminated due to toxicity in preclinical species while AZD7325 and PF-06372865 did not achieve efficacy endpoints in patients. We highlight a new compound, KRM-II-81, that is an imidazodiazepine selective for GABAAR containing α2/3 and β3 proteins. In preclinical studies KRM-II-81 produced anxiolytic-like effects but with minimal sedation, respiratory depression, and abuse liability. Thus, KRM-II-81 is a newly discovered, non- BZD anxiolytic compound, which targets a selective population of GABAAR for improved therapeutic gain and reduced side effects.

Use of Gabapentin or Alprazolam in Cats during Postoperative, Short-Term Hospitalization.

This prospective, randomized study aimed to assess the anxiolytic efficacy of gabapentin or alprazolam in cats during short-term postoperative hospitalization. Sixty cats were randomly assigned to three groups (gabapentin-treated [100 mg per cat], alprazolam-treated [0.125 mg per cat], or placebo-treated), with treatments administered twice daily for two days. Stress levels were evaluated using Cat Stress Scores, serum cortisol, and glucose concentrations. Pain scores, food consumption, and adverse effects such as sedation were also monitored. Fifty-five cats completed the study. Both medications demonstrated similar reductions in stress levels. Cats receiving gabapentin had lower pain scores, while those receiving alprazolam exhibited significantly increased food intake on the first postoperative day. However, both medications resulted in comparable levels of sedation. In the context of postoperative hospitalization, pharmacological intervention with anxiolytics could be effective in reducing stress levels. Despite potential side effects, gabapentin and alprazolam may contribute to an improved quality of short-term hospitalization for cats.

Synergistic anxiolytic efficacy exploring the combined effects of diazepam and zinc chloride in wistar albino rats.

Combinations of medications are frequently employed when their effects are similar. Beyond aiding in the reduction of medication dosages, this approach may yield additional positive outcomes. Studies have shown that zinc can mitigate anxiety-related behavior in laboratory animals. This study aimed to investigate the potential stabilizing effects of zinc chloride and diazepam in Wistar albino rats.Five groups, each comprising six animals. Test groups included two combinations of zinc chloride and diazepam, each with two different doses of diazepam (1 and 2 mg/kg) and 10 mg/kg of zinc chloride. Four established anxiety models-the Elevated Plus Maze (EPM), the hole board, the light and dark box, and the mirror chamber-were employed to assess the anxiolytic effects. The combination of zinc chloride and diazepam proved to be more effective than the individual doses of zinc chloride and diazepam, indicating enhanced anxiolytic effects.

Clinical Evaluation of Oral Midazolam Containing Cyclodextrin in Pediatric Magnetic Resonance: A Retrospective Cohort Study.

Reducing a child's level of anxiety before magnetic resonance imaging (MRI) procedures allows for better behavioral outcomes. The aim of this retrospective study was to evaluate anxiolytic efficacy of Midazolam/γ-cyclodextrin oral formulation. We retrospectively reviewed 100 medical charts of children who, between 1 February and 31 July 2022, underwent MRI under general anesthesia with or without premedication with midazolam/γ-cyclodextrin. Primary outcome was comparison of behavior to facemask positioning, while secondary endpoints were degree of drugs acceptance, anxiolytic effect evaluation, child's behavior on separation, and sevoflurane need. Facemask positioning was accepted by 58% of the midazolam/γ-cyclodextrin group compared to 22% of children in the control group. The rate of acceptance was >90%. At the moment of separation from parent, none of the premedicated children needed to be restrained compared to 18% in the control group. A lower percentage of sevoflurane was needed for eye-closure at induction of anesthesia and for anesthesia maintenance. At emergence from anesthesia, 46% of children in the premedicated group compared to 66% of children in the control group showed transient agitation. Midazolam/γ-cyclodextrin showed a good profile of acceptance, satisfactory anxiolytic properties, and reduced need for anesthetics when administered to children before MRI under general anesthesia.

Design, synthesis, and evaluation of anxiolytic activity of 2-(4-phenylpiperazin-1-yl)-1H-benz[d]imidazole and 2-(4-phenylpiperazin-1-methyl)-1H-benz[d]imidazole derivatives

BackgroundIn contemporary society, anxiety has become a widespread disorder leading to compromised well-being and heightened depressive states. Extensive literature reviews indicate the diverse biological effects of benzimidazole and piperazine derivatives, notably their impact on the central nervous system. This study aimed to design, molecularly dock, synthesize, and assess the anxiolytic potential of six derivatives of 2-(4-phenylpiperazin-1-yl)-1H-benz[d]imidazole and 2-(4-phenylpiperazin-1-methyl)-1H-benz[d]imidazole.ResultsIn the present study, an attempt was made to synthesize benzimidazole derivatives conventionally. The benzimidazole nuclei are condensed with various substituted piperazines to obtain targeted benzimidazole–piperazine hybrids. Their anxiolytic activity is determined using the Elevated Plus Maze test and hole board test in mice. All compounds have shown good docking scores and in vivo anxiolytic activity.ConclusionOut of all the derivatives synthesized, compounds 5b, 5c, and 5f exhibited outstanding anxiolytic efficacy in both computational simulations and live subjects. Compound 5b demonstrated a remarkable docking score relative to the ligand, suggesting its potential as a promising candidate warranting further exploration.

Relationship between COMT Gene Polymorphism, Anxiety, and Pain Perception during Labour.

The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. The present study investigates the existence of anxiety and pain perception in relation to the COMT (catechol-O-methyltransferase) gene polymorphism in labouring women (during "natural" childbirth) with or without inhaled analgesia. A total of 181 women who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n = 90) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group (n = 91) without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. The pain perception of parturients was self-evaluated two times according to the VAS (Visual Analogue Scale), and anxiety as a personality trait was determined with the STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. In the 181 pregnant women, there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygotes (AA). A negative association of pain perception with the GA (mutant heterozygote) polymorphism of the COMT gene versus the wild-type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and GG. The difference reached statistical significance only when comparing AA versus GA (p > 0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4-7). The COMT gene polymorphism was associated with pain perception and anxiety among parturients. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in parturients with the COMT gene polymorphism AA.

Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder.

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD's potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD's beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied. Here, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors. We observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends. Our results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD.

11-Ethoxyviburtinal improves chronic restraint stress-induced anxiety-like behaviors in gender-specific mice via PI3K/Akt and E2 /ERβ signaling pathways.

Anxiety disorder is a chronic and disabling psychiatric disorder that is more prevalent in females than in males. 11-Ethoxyviburtinal is an iridoid extracted from Valeriana jatamansi Jones, which has anxiolytic potential. The aim of the present work was to study the anxiolytic efficacy and mechanism of 11-ethoxyviburtinal in gender-specific mice. We first evaluated the anxiolytic-like efficacy of 11-ethoxyviburtinal in chronic restraint stress (CRS) mice of different sexes through behavioral experiments and biochemical indexes. In addition, network pharmacology and molecular docking were used to predict potential targets and important pathways for the treatment of anxiety disorder with 11-ethoxyviburtinal. Finally, the influence of 11-ethoxyviburtinal on phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, estrogen receptor β (ERβ) expression, and anxiety-like behavior in mice was verified by western blotting, immunohistochemistry staining, antagonist intervention methods, and behavioral experiments. 11-ethoxyviburtinal alleviated the anxiety-like behaviors induced by CRS and inhibited neurotransmitter dysregulation and HPA axis hyperactivity. It inhibited the abnormal activation of the PI3K/Akt signaling pathway, modulated estrogen production, and promoted ERβ expression in mice. In addition, the female mice may be more sensitive to the pharmacological effects of 11-ethoxyviburtinal. 11-ethoxyviburtinal may exert its anxiolytic-like effects through PI3K/Akt and E2/ERβ signaling pathways. Meanwhile, by comparing the male and female mice, gender differences may affect the therapy and development of anxiety disorder.

Pharmacognostical, Phytochemical Screening and Evaluation of Anxiolytic activity of Alcoholic Extract of Withania somnifera (L) Dunal Roots

The roots of Withania somnifera (L) Dunal (W. somnifera) are used extensively in Ayurveda, the classical Indian system of medicine, and W. somnifera is categorized as a rasayana, which are used to promote physical and mental health, to provide defense against disease and adverse environmental factors and to arrest the aging process. W. somnifera has been used to stabilize mood in patients with behavioural disturbances. The objective of this study was to investigate pharmacognostical, phytochemical features and anxiolytic activity of alcoholic extracts of W. somnifera roots. The various pharmacognostical variables were assessed using generally accepted techniques with certain variations. An established test technique that is documented in the literature was used to determine the qualitative analysis of different phytochemical elements. The anxiolytic efficacy of the alcoholic extract of W. somnifera roots in mice was evaluated using the elevated plus maze test (EPMT), light and dark test (L and DT), and open field test (OFT). Extract dosages of 250, 500, and 750 mg/kg were compared to the recommended dosage of diazepam (1 mg/kg) to determine its efficacy. Alcoholic extract underwent phytochemical examination, which identified the presence of fixed oils, lipids, proteins, amino acids, carbohydrates, tannins, and phenolics. The percentage of time spent and the number of entries in the open arm in EPMT were both considerably enhanced by the alcoholic extract of W. somnifera roots (250, 500, 750mg/kg, p.o.). The extract significantly increased time spent, the frequency of crossings, and decreased the length of immobility in the light box in L and DT. The extract in OFT significantly increased the number of rearings, increased ambulation, and decreased self-grooming and faecal dropping all signs of exploratory behaviour. The findings of the current investigation provide scientific support for the traditional use of W. somnifera by indicating that an alcoholic extract of its roots may have anxiolytic properties.&#x0D; Keywords: Anxiolytic, Withania somnifera (L) Dunal, Elevated plus maze, Open field test, Light and dark test

A Comparative Evaluation of the Anxiolytic Effect of Oral Midazolam and a Homeopathic Remedy in Children During Dental Treatment.

Background Midazolam is recommended by many health standards. However, there is no compelling evidence that midazolam has anti-anxiety effects in children. Homeopathy can be one of the mainstays for effective child management while reducing negative side effects. The aim of the study was to evaluate the anxiolytic efficacy of midazolam (oral) and homeopathic remedies in children during dental treatments. Methodology The current ex-vivo study was conducted in the department of Pedodontics and Preventive Dentistry department of a private dental institution. A total of 48 children aged four to 14 years were selected based on the inclusion and exclusion criteria. The participants were evenly and randomly divided into groups A and B using the lottery method. Group A: 20 minutes previous to the treatment, a right blend of an equal volume of 0.5mg/kg injectable solution of midazolam hydrochloride. Group B: Received Aconite napellus (homeopathic remedy). Results During anxiety, the hypothalamic pituitary adrenal axis gets activated which causes a release of body fluids including salivary cortisol levels. Salivary amylase also responds quickly during stress and anxiety by increasing its levels. Midazolam is used in Dentistry to reduce anxiety as it is able to reduce salivary cortisol and amylase levels.Aconite napellus being homeopathic remedy is useful in Dentistry to reduce salivary cortisol and amylase levels which is observed in the present study. There was a decrease in salivary cortisol and amylase concentrations following midazolam (8.51 ± 6.7) (41.48 ± 23.8) and Aconite napellus (homeopathic remedy) (7.53 ± 5.2) (37.08± 22.8) administration, as well as a decrease in heart rate, systolic and diastolic blood pressure. Furthermore, all of the differences were statistically significant (p<0.05). Conclusion In children with behavioral difficulties, homeopathic remedy was marginally more successful than oral midazolam in lowering anxiety during dental treatment.

Walking the Benzodiazepine High Wire.

The number of benzodiazepine (BZD) prescriptions has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose. These increases have prompted the U.S. Food and Drug Administration to update its "boxed warning" and have caused organizations to revisit prescribing guidelines. Concurrently, strong evidence from clinical trials supports the anxiolytic efficacy of BZDs. Although antidepressants and psychotherapy remain preferred treatments for chronic anxiety, BZDs remain helpful in treating acute or severe and persistent anxiety that does not respond to first-line therapy. Provider and patient education, coupled with prescribing surveillance, may be preferable to an overly stringent regulatory approach to guiding BZD use.

Analgesic and Anxiolytic Effects of Virtual Reality During Minor Procedures in an Emergency Department: A Randomized Controlled Study

We aimed to assess the analgesic and anxiolytic efficacy of distraction, a nonpharmacologic intervention provided by 3-dimensional (3D) virtual reality (VR) compared with that provided by 2-dimensional (2D) VR during minor emergency department (ED) procedures. This randomized controlled study conducted in the ED of a teaching hospital included patients aged more than or equal to 18 years undergoing minor procedures. The patients watched the same computer-generated VR world either in 3D in a head-mounted display (intervention) or in 2D on a laptop screen (control). Our main outcomes were pain and anxiety during the procedure, assessed on a 100-mm visual analog scale. Secondary outcomes included the impression of telepresence in the computer-generated world assessed using the Igroup Presence Questionnaire, and the prevalence and intensity of cybersickness measured on a 100-mm visual analog scale. The final analysis included 117 patients. The differences in median procedural pain and anxiety levels between the 2D and 3D VR groups were not significant:-3 mm (95% confidence interval [CI]-14 to 8) and-4 mm (95% CI-15 to 3), respectively; the difference in telepresence was 2.0 point (95% CI 0 to 2.0), and the proportion difference of cybersickness was-4% (95% CI-22 to 14), with an intensity difference of-5 mm (95% CI-9 to 3). During minor procedures in adult patients in the ED, distraction by viewing a 3D virtual world in a head-mounted VR display did not result in lower average levels of procedural pain and anxiety than that by 2D viewing on a screen despite a higher sense of telepresence. There were no significant differences in the prevalence and intensity of cybersickness between the 2 groups.

Beneficial effects of Silexan on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders: randomized, placebo-controlled trials revisited

Silexan is a proprietary active substance produced from Lavandula angustifolia, with proven anxiolytic efficacy in subthreshold and generalized anxiety disorder as well as in mixed anxiety and depressive disorder with beneficial impact on anxiety-related sleep disturbances. The pharmacological profile and clinical observations suggest that Silexan may also have an antidepressant effect. To investigate the effect of Silexan on co-occurring depressive symptoms, we present a meta-analysis of the five placebo-controlled clinical trials hitherto performed with Silexan in subthreshold anxiety (n = 3) and anxiety disorders (n = 2). Patients of all trials received Silexan 1 × 80 mg/day or placebo for 10 weeks according to random assignment. Assessment of the antidepressant effect was based on item ‘depressed mood’ from the Hamilton Anxiety Rating Scale (HAMA) administered in all trials and on the total scores of the Montgomery Åsberg Depression Rating Scale (MADRS) or the Hamilton Depression Rating Scale (HAMD) used in three trials. After 10-week treatment, patients receiving Silexan showed significantly more pronounced score reduction for HAMA item ‘depressed mood’ than those in the placebo group (p = 0.01). Significant superiority of Silexan over placebo could also be shown for mean MADRS or HAMD total score reduction (three studies; p < 0.01). Silexan-treated patients with more severe depressive symptoms at baseline showed more pronounced improvements than those with milder symptoms. Our meta-analysis clearly shows that Silexan has a beneficial effect on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders and may, hence, lead to important therapeutic implications for depressive disorders.

Development and Screening of Anxiolytic and Antistress activity of Novel Health Promoting Tea Fortified with Herbs

The current investigation was planned to assess anxiolytic and antistress properties of polyherbal formulation containing ethanolic extracts of four plants Withania somnifera (Ashwagandha), Justicia adhatoda (Vasaka), Trigonella foenum (Methi), Vitis vinifera (Grape seed) and to develop a tea fortified with these herbs. The anxiolytic efficacy was determined with the adult rats by elevated plus maze (EPM) analysis and motor coordination with the rotarod test. The antistress activity was evaluated with the adult rats by swimming endurance test (SET), anoxia tolerance test (ATT), and immobilization stress test (IST). In EPM, Polyherbal extract (PHE 200 mg/kg; 400 mg/kg) significantly increased the percentage of time spent in open arms (180.33±4.89 and 202.67±3.68 seconds) in a dose dependent manner as compared to the control group (39.00±3.88 seconds) and is comparable with the standard diazepam (226.67±2.98 seconds). In RotaRod test, the polyherbal extract significantly diminished spontaneous activity (fall off time with control rats is 43.16±2.05 seconds and with polyherbal extract 400 mg/kg treated rats is 203.33±2.21 sec). In swimming endurance, polyherbal extract displayed a dose-dependent decrease in immobility time (71.66±3.45 sec) which is almost comparable to standard antistress medicine Mentat (62.66±3.13 sec). In anoxia tolerance test polyherbal extract increased the convulsion time which was again statistically significant. The levels of neurotransmitters serotonin, dopamine and norepinephrine were found to be increased with the polyherbal extract. The present study reveals that polyherbal extract possesses significant anxiolytic and anti-stress activity and, an herbal tea was prepared using polyherbal extract for the management of stress.

Odors associated with neonatal experiences with the dam have enhanced anxiolytic effects in rat

Odor stimuli are widely reported to promote relaxation and reduce anxiety in humans and rodents. However, it remains unclear if this anxiolytic efficacy can be further enhanced by association with positive experiences. Therefore, we compared the effects of a novel odor to a familiar odor previously paired with a positive experience on anxiety-like behaviors in rats. One group of Wistar-Imamichi female and male pups was exposed to an odor stimulus with their dams during postnatal days (PNDs) 8-12, whereas another control group was exposed to perfused air during the same period. Starting on PND 42, all animals were examined in the open field test (OFT) and elevated plus maze (EPM) test during exposure to scent-free air (vehicle), a novel odor, or the positive-familiar odor from postnatal exposure. In the EPM, female rats entered open arms with all 4 paws (complete entry) more frequently and spent more time on open arms during exposure to the positive-familiar odor than during exposure to air or a novel odor, whereas partial open arm entries with forepaws only were increased during exposure to both novel and positive-familiar odors compared to air. In contrast, male rats demonstrated no significant increase in open arm activity during positive-familiar odor exposure, but did show equally reduced grooming frequency during novel and familiar-positive odor exposure in the OFT. Exposure to positive-familiar odors may be an effective and safe method for anxiety reduction, especially in females.

Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice

Objective: Evaluation of anxiolytic and anti-depressant activity of Neolamarckia cadamba in mice.&#x0D; Material &amp; Method: The aqueous and methanolic extract of “Neolamarckia cadamba” and chose low medium and high doses for therapy. The behavioral consequences of an oral acute or subacute (10 days) treatment. Neolamarckia cadamba (250 and 500 mg/kg, p.o) aqueous and methanolic stem bark extract assessed in male and female Swiss mice (EPM). Diazepam (1 mg/kg) will also be evaluated. Anti-anxiety drug testing in the lab.&#x0D; Results: Neolamarckia cadamba, acute oral toxicity was detected with different extracts (ENC &amp; AQNC) having dose (5, 50, 300, 1000 mg/kg ) via the oral route, shows no change in behavioral responses and observation shows no acute oral toxicity. Hence depending upon it, Dose was selected 250 mg/kg &amp; 500 mg/kg for our experimental work.&#x0D; Conclusion: Neolamarckia cadamba has both anxiolytic and antidepressant properties, which likely operate through BZD receptors, selective serotonin reuptake inhibitors. The antidepressant and anxiolytic properties of Neolamarckia cadamba ethanolic and aqueous extracts were investigated in Swiss albino mice at doses of 250 and 500 mg/kg, respectively. Both extracts (ANC &amp; ENC) showed strong antidepressant and anxiolytic efficacy using TST and EPM parameters.

Bidirectional Influence of Limbic GIRK Channel Activation on Innate Avoidance Behavior.

Systemic administration of ML297, a selective activator of G-protein-gated inwardly rectifying K+ (GIRK) channels, decreases innate avoidance behavior in male C57BL/6J mice. The cellular mechanisms mediating the ML297-induced suppression of avoidance behavior are unknown. Here, we show that systemic ML297 administration suppresses elevated plus maze (EPM)-induced neuronal activation in the ventral hippocampus (vHPC) and basolateral amygdala (BLA) and that ML297 activates GIRK1-containing GIRK channels in these limbic structures. While intracranial infusion of ML297 into the vHPC suppressed avoidance behavior in the EPM test, mirroring the effect of systemic ML297, intra-BLA administration of ML297 provoked the opposite effect. Using neuron-specific viral genetic and chemogenetic approaches, we found that the combined inhibition of excitatory neurons in CA3 and dentate gyrus (DG) subregions of the vHPC was sufficient to decrease innate avoidance behavior in the EPM, open-field, and light-dark tests in male C57BL/6J mice, while performance in the marble-burying test was not impacted. Furthermore, genetic ablation of GIRK channels in CA3/DG excitatory neurons precluded the suppression of avoidance behavior evoked by systemic ML297 in the EPM test. Thus, acute inhibition of excitatory neurons in the ventral CA3 and DG subregions of the vHPC is necessary for the apparent anxiolytic efficacy of systemic ML297 and is sufficient to decrease innate avoidance behavior in male C57BL/6J mice.SIGNIFICANCE STATEMENT We interrogated the cellular mechanisms underlying the apparent anxiolytic efficacy of ML297, a selective activator of G-protein-gated inwardly rectifying K+ (GIRK) channels and promising lead compound. Intracranial infusion of ML297 into the ventral hippocampus (vHPC) and basolateral amygdala (BLA) complex exerted opposing influence on innate avoidance behavior in male C57BL/6J mice, the former recapitulating the suppression of avoidance behavior evoked by systemic ML297. Using viral genetic and chemogenetic approaches, we showed that combined inhibition of excitatory neurons in CA3 and dentate gyrus (DG) subregions of the vHPC is sufficient to decrease innate avoidance behavior in male mice and mediates the decrease in avoidance behavior evoked by systemic ML297. These findings establish a foundation for future investigations into the therapeutic potential of GIRK channel modulation in anxiety disorders.

The anxiolytic effect of some plant extracts in clinical trials and animal models

The phenomenon of anxiety remains poorly understood and there is much to be learnt about its’s effective treatment. Here we discuss the data of available scientific literature concerning the use of plant derived extracts in the treatment of anxiety. Study of the treating effects of natural alternatives to prescription drugs is very important in regard to limitations of current drug therapies. Significance of the study of treating efficacy of endemic plant species, endemic to Georgia in particular, and the use of animal models, such as rat grooming and rat behavior in maze, for evaluation of the anxiolytic efficacy of phytomedicines is discussed as well. We conclude, that medical as well as experimental trials in animal models of anxiety provide strong argument for the use of plant extracts as an alternative to the current drug therapies for anxiety.