Experimental Models Of Anxiety Research Articles

Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST). Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs. The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo. Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Animals Use to Find Anxiolytic Activity: An Updated Review with Advantage of Each Model

Anxiety affects both humans and animals in profound ways, and understanding its psychological and biological components is essential to the development of anxiolytic medications. Animal models are utilized as simulations to explain emotional activities and as screening tools in anxiety research. Rats are the animal model used most often; mice, a more genetically flexible mammal, do less well in animal models. Behavioral investigations need careful consideration of changeable characteristics related to handling, climate, or models. To help us better understand the neurobiological elements of anxiety, the most recent experimental anxiety models such as the elevated plus maze apparatus, light-dark model, open field apparatus, and hole board apparatus are being examined. Psychopharmacological disorders affect one in seven Indians; nevertheless, adverse effects include weight gain, cramping in the muscles, dysphoria, upset stomach, blurred vision, and issues with blood tests may occur. In order to improve our knowledge of the animal models used to determine the anxiolytic action in mice, we will talk about pertinent animal models that have been established in this article.
 Keywords: Anxiolytic activity, Anxiety, Elevated zero maze, Plus maze, Elevated T maze, light and dark box model and Mirrored chamber, Animal models

Animal models of anxiety: a review

Anxiety is a disorder that affects the quality of life and also imposes a huge economic burden. Animal models of anxiety have widened our understanding of the pathophysiology behind anxiety and to identify newer pharmacological compounds. Every behavioral test has its own limitations, and there are ways to minimize these like environment and handling. This review lists various experimental models of anxiety based on unlearned ethological models, learned responses like the Vogel conflict test, and psychological and physical stress models.

Essential Oils in Experimental Models of Neuropsychiatric Disorders: A Systematic Review.

Background Neural cells undergo functional or sensory loss due to neurological disorders. In addition to environmental or genetic factors, oxidative stress is a major contributor to neurodegeneration. In this context, there has been a growing interest in investigating the effects of EOs (EOs) in recent years, especially in the treatment of neuropathologies. The chemical and biological effects of EOs have led to important treatment tools for the management of various neurological disorders.Objective In the present study we performed a systematic review that sought to comprehend the neuroprotective effects of different EOs.Method This work is a systematic review where an electronic search was performed on PubMed, ScienceDirect, Cochrane Library and SciELO (Scientific Electronic Library Online) databases, covering the last 10 years, using “Essential oil” and “Neuroprotective effect” as reference terms.Results A total of 9 articles were identified, in which the efficacy of EOs was described in experimental models of anxiety, dementia, oxidative stress, cerebral ischemia, Alzheimer’s disease, and oxidative toxicity.Conclusion EOs from different species of medicinal plants have shown positive responses in neurological disorders such as anxiety, dementia, oxidative stress, cerebral ischemia, and oxidative toxicity. Thus, EOs emerges with the potential to be used as alternative agents in the treatment of neurological disorders.

Efficacy of Aconite and Ignatia as an anxiolytic- In vivo study

Anxiety disorders are the most common form of psychiatric disorders and start at an early age. The homeopathic system of complementary treatment is increasingly used by the general population. Ultra-diluted Aconite and Ignatia are homeopathic medicines used by clinicians for the treatment of anxiety. The objective of this study is to test the efficacy of Aconite 12CH and Ignatia 12CH on experimental anxiety models of Wistar rats subjected to chronic unpredictable stress. 30 Wistar rats were divided into 5 groups of Control, Stress, Vehicle, Aconite and Ignatia group with 6 animals in each group. All the groups were subjected to chronic unpredictable stress except the control group. The last two groups were fed Aconite and Ignatia through oral gavage daily for 5 weeks. Following this, a behavioral and biochemical assessment was done. It was observed that the Aconite and Ignatia treated animals showed better weight gain, but the behavioral and biochemical assessment did not show any significant change. Hence it was inferred that ultra-diluted Aconite and Ignatia though an anxiolytic used clinically, did not decrease anxiety in Wistar rats which were subjected to chronic unpredictable stress.

Anxiolytic activity of ultra-diluted Aconitum napellus on Wistar rats

Background: Anxiety disorders are highly prevalent that affect millions of people worldwide. Homeopathic system is gaining popularity due to its efficacy in chronic diseases. Ultra-diluted Aconitum napellus is a homeopathic medicine used by clinicians for treatment of acute anxiety.
 Aim: Objective of this study is to test the efficacy of Aconite on experimental anxiety models of Wistar rats. Methodology: 18 Female Wistar rats were divided into Control, Anxiety, and Anxiety + Aconite (ANX+ACO) groups. Acute stress was induced by restraining the rats for six hours daily for five days in Anxiety and ANX + ACO groups. After five days of stress, a single dose of Aconite 200cH was given to ANX + ACO group through oral gavage, whereas control and anxiety group rats were maintained with a normal diet. Following this, behavioral assessment was done. Results: It was observed that the Aconite treated group had more number of entries and also the percentage of time spent in the open arm was higher than the stressed anxiety group. Histological study of the brain tissue procured from all three groups was analyzed. Conclusion: It was inferred that ultra-diluted homeopathic Aconite has decreased anxiety in Wistar rats which were subjected to acute restrain stress.

Potential of an aqueous extract of Lippia multiflora Moldenke (Verbenaceae) in the treatment of anxiety disorders: Possible involvement of serotoninergic transmission

Ethnopharmacological relevance: The leaves and stems of Lippia multiflora Moldenke (Verbenaceae) are used in traditional medicine to treat depression, anxiety and epilepsy. Aim of the study: The present study investigated the anxiolytic-like effects of Lippia multiflora aqueous extracts in experimental models of anxiety. Materials and methods: Elevated plus maze and open field tests were used to evaluate anxiety and exploratory behaviour. The possible mechanism of action of Lippia multiflora were investigated after pretreatment of animal with agonist and antagonist of serotonin receptors, such as: mCPP, a partial agonist at the 5-HT2C receptors; Way-100635, a selective 5-HT1A receptors antagonist; and DOI, the 5-HT2A/2C receptors agonist. The levels of monoamine neurotransmitters were evaluated in the brain. Results: In the elevated plus maze, Lippia multiflora increased the number of entries into and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. These effects were blocked with the agonist and antagonist of serotonin receptors. In the open field, Lippia multiflora increased crossing and reduced rearing and defecation. The endogenous levels of noradrenaline, dopamine and serotonin in the brain homogenates remain comparable to that distilled water-treated animals. Conclusion: It could be concluded that Lippia multiflora aqueous extracts, used in traditional medicine in Cameroon for the treatment of depression, anxiety and epilepsy seemed to possess anxiolytic properties in mice. These effects might be mediated by serotonin receptors, but not by modulation of the levels of monoamine neurotransmitters when the extract is administered once after one hour.

A plausible involvement of GABAA/benzodiazepine receptor in the anxiolytic-like effect of ethyl acetate fraction and quercetin isolated from Ricinus communis Linn. leaves in mice

Ricinus communis Linn. (Euphorbiaceae) leaves are used in Indian traditional medicine to treat inflammatory and central nervous disorders. The polyphenolic compounds like quercetin (QUR), gallic acid, and rutin display an anxiolytic-like activity. These constituents are also present in Ricinus communis leaves; however there are no scientific investigations conducted to verify the anxiolytic-like effects of ethyl acetate fraction of Ricinus communis (RCLEA) leaves. HPLC technique was used to quantify the polyphenols contained in RCLEA fraction. It revealed the contents (% w/w): gallic acid (0.63), rutin (4.36), QUR (1.62) and Pyrogallol (PYR) (14.07). The present study investigated the anxiolytic-like effects of RCLEA fraction and two major polyphenols in Ricinus communis in experimental models of anxiety compared with a positive control diazepam (DZP) (1 mg/kg, i.p.). In order to investigate the anxiolytic-like effect, doses of RCLEA fraction (25, 50 and 100 mg/kg, i.p), QUR and PYR (1, 5 and 10 mg/kg respectively, i.p.) were administered to mice and subjected to open field test (OFT), elevated plus maze (EPM) or rota-rod test. The results of OFT revealed the significant increase in time spent in central area with treatments of RCLEA fraction (50 and 100 mg/kg, p < 0.05 and p < 0.01 respectively), QUR (10 mg/kg, p < 0.05) and PYR (10 mg/kg, p < 0.05). The reduction in rearings was observed with doses of RCLEA fraction, QUR and PYR. Significant reductions were found in defecation after treatments of RCLEA fraction and QUR and comparable to DZP. The results of OFT were further validated using EPM, showed that RCLEA fraction and QUR treatments (50 and 10 mg/kg, respectively) produced a significant increase in the time spent and entry into the open arms of elevated plus maze, with a profile comparable to that of DZP. No significant changes were observed in the rota-rod test, suggesting that the RCLEA fraction, QUR and PYR did not cause neurotoxicity, sedation and muscle relaxation commonly related to benzodiazepines. RCLEA fraction and QUR presented anxiolytic-like effect on the EPM, which was partially reversed by flumazenil suggested involvement of GABAA/benzodiazepine receptor. These results suggest that RCLEA fraction and QUR exerts anxiolytic-like effects, and its mechanism of action appears to be modulated by GABAA/benzodiazepine receptor also supported by molecular docking study.

Synthesis and Anxiolytic Activity of some novel benzotriazole derivatives

1,2,3-Benzotriazole (BTA) is a heterocyclic compound with three nitrogen atoms. It is a polar and colourless compound which can be used for its great versatility. The enormous investigations on derivatives of benzotriazole reveal wide applicability for tagging and delivering a number of heterocyclic nuclei with this molecule. In the present work synthesis of several derivatives of 2-(substituted)-5-[(N-benzotriazolomethyl)-1,3, 4-thiadiazolyl]- imidazole-2-thione has been synthesized and are evaluated for their anxiolytic activity. The antianxiety activities of the synthesized derivatives were evaluated using EPM test and Bright and dark box test experimental models of anxiety. All results were expressed as mean± standard error mean (SEM) and analysed by one-way ANOVA. Post-hoc comparisons were performed by applying Dunnet’s test. P &lt;0.05 was considered statistically significant.&#x0D; Keywords: Benzotriazole; Thiadiazole; Thiazolidinone; Anxiolytic Activity; Anxiety; Elevated Plus Maize; Bright and Dark Arena.

Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences.

Animal models of anxiety disorders are important for elucidating neurobiological defense mechanisms. However, animal models are limited when it comes to understanding the more complex processes of anxiety that are unique to humans (e.g., worry) and to screen new treatments. In this review, we outline how the Experimental Psychopathology approach, based on experimental models of anxiety in healthy subjects, can mitigate these limitations and complement research in animals. Experimental psychopathology can bridge basic research in animals and clinical studies, as well as guide and constrain hypotheses about the nature of psychopathology, treatment mechanisms, and treatment targets. This review begins with a brief review of the strengths and limitations of animal models before discussing the need for human models of anxiety, which are especially necessary to probe higher-order cognitive processes. This can be accomplished by combining anxiety-induction procedures with tasks that probe clinically relevant processes to identify neurocircuits that are potentially altered by anxiety. The review then discusses the validity of experimental psychopathology and introduces a methodological approach consisting of five steps: (1) select anxiety-relevant cognitive or behavioral operations and associated tasks, (2) identify the underlying neurocircuits supporting these operations in healthy controls, 3) examine the impact of experimental anxiety on the targeted operations in healthy controls, (4) utilize findings from step 3 to generate hypotheses about neurocircuit dysfunction in anxious patients, and 5) evaluate treatment mechanisms and screen novel treatments. This is followed by two concrete illustrations of this approach and suggestions for future studies.

Effect of ethanol Adiantum capillus-veneris extract in experimental models of anxiety and depression

Depression is one of the most common psychiatric disorders with a prevalence of 15%-25%. Monoamine aminotransferases, in particular, norepinephrine, serotonin, and dopamine, change in the brain of depressed people. Adiantum capillus-veneris is one of the species of the maidenhair fern genus that have traditionally been used to treat cough, cold symptoms, and local hair loss.In this experimental study, white male rats weighing 250-300 g were assigned to 5 groups of 10 each; group 1: Receiving normal saline; groups 2-4: Receiving A.capillus-veneris extract at 50, 100, and 200 mg/kg, respectively; and group 5: Receiving fluoxetine at 10 mg/kg. Chronic unpredictable stress (CUS) was induced by 3-week exposure to chronic stress. The forced swim test and plus maze were used to assess depression and anxiety, respectively. Malondialdehyde (MDA) levels and antioxidant capacity in the serum and brain were measured. Treatment with A.capillus-veneris extract at 200 mg/kg significantly reduced the duration of immobility. In the group given extract at 200 mg/kg, a significant increase in the number of open arm entries was observed when compared to the control group. A.capillus-veneris extract at 50, 100, and 200 mg/kg resulted in a significant increase in the time spent in the open arm. A.capillus-veneris extract reduced MDA levels and increased antioxidant levels of serum and brain in rat. A.capillus-veneris has significant antidepressant and anti-anxiety effects in rat, probably due to its antioxidant and anti-inflammatory activities.

The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons. Chronic administration of both paroxetine and alprazolam decreased these responses with morphological correlates between the panicolytic effect of both drugs administered at the highest dose and decreases in Fos protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and periaqueductal gray matter columns, which are structures that make up the encephalic aversion system. These findings provide face, construct and predictive validities of this new experimental model of anxiety- and panic attack-like behavioral responses displayed by threatened prey confronted with venomous coral snakes.

Anti-anxiety activity of ethanolic extract of Spermacoce hispida leaves in swiss albino mice

Background: The objective of the study was to evaluate the anxiolytic activity of ethanolic extract of Spermacoce hispida (EESH) in swiss albino mice.Methods: Forty eight adult Swiss albino mice weighing 25-30grams were selected. 24 were allocated to Elevated plus maize test and the remaining 24 to Bright and dark box test models. In each model, there were 4 groups. The control group received normal saline (10ml/kg), the standard, Diazepam (1mg/kg) and test groups received ethanolic extract of Spermacoce hispida (100mg/kg, 200mg/kg p.o. respectively) 1h prior to the acute study. In chronic study the drugs were given orally once a day for 10 days and the last dose was given 1h before the experiment. The antianxiety activity of the test drug was evaluated using EPM test and Bright and dark box test experimental models of anxiety. All results were expressed as mean±standard error mean (SEM) and analysed by one-way ANOVA. Post-hoc comparisons were performed by applying Dunnet’s test. P &lt;0.05 was considered statistically significant.Results: Ethanolic extract of Spermacoce hispida significantly increased the duration of time spent and number of entries in open arm in EPM and increased the number of entries into the bright arena, the time spent and the rears in bright arena indicating anxiolytic activity and EESH 200 mg/kg was found to be better than diazepam.Conclusions: The results of the present study suggest that the ethanolic extract of Spermacoce hispida have anxiolytic activity better than Diazepam.

Discovery of 4-amino-3-arylsulfoquinolines, a novel non-acetylenic chemotype of metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulators

Negative allosteric modulators of metabotropic glutamate receptor 5 (mGlu5) showed efficacy in a number of animal models of different CNS diseases including anxiety and depression. Virtually all of the compounds which reached the clinic belong to the same chemotype having an acetylenic linker that connects (hetero)cyclic moieties. Searching for new chemotypes we identified a morpholino-sulfoquinoline derivative (1) by screening our corporate compound deck. The HTS hit showed reasonable affinity and selectivity towards mGlu5 receptors, however, its inferior metabolic stability prevented its testing in vivo. In a chemical program we aimed to improve the affinity, physicochemical properties and metabolic stability exploring three regions of the hit. Systematic variation of different amines at position 4 (region I) led to the identification of 4-methyl-piperidinyl analogues. Substituents of the quinoline core (region II) and the phenylsulfonyl moiety (region III) were mapped by parallel synthesis. Evaluation of both morpholino- and 4-methyl-piperidinyl-sulfoquinoline libraries of about 270 derivatives revealed beneficial substituent combinations in regions II and III. Blood levels of optimized 4-methyl-piperidinyl-sulfoquinolines, however, were still insufficient for robust in vivo efficacy. Finally, introducing 4-hydoxymethyl-piperidinyl substituent to region I resulted in new sulfoquinolines with greatly improved solubility and reasonable affinity coupled with affordable metabolic stability. The most promising analogues (24 and 25) showed high blood levels and demonstrated significant efficacy in the experimental model of anxiety.

Effects of Musa sapientum stem extract on experimental models of anxiety.

The Musa sapientum (banana) plant extract has shown antioxidant activity in previous studies. Oxidative stress is one of the important factors implicated in the pathogenesis of anxiety disorders. The present study aimed to evaluate the anxiolytic activity of aqueous extract of M. sapientum stem (MSSE) in experimental models in mice. Elevated Plus Maze method and locomotor monitoring by photoactometer were used. Animals were divided into five different groups (n=6/group). The vehicle, standard and the experimental groups were given distilled water (10 ml/kg), diazepam (1 mg /kg intraperitoneally) and incremental doses of 25, 50 and 100 mg/kg of MSSE, respectively, prior to the experiment. The standard group received diazepam. The number of open arm entries and the duration of time spent in the open arms in the MSSE-treated groups increased significantly in a dose-dependent manner as compared to that of control group. The duration of time spent in closed arms in the MSSE-treated groups decreased significantly in a dose-dependent manner as compared to that of the control group. MSSE also decreased the locomotor activity significantly at all three test doses. The results of this study suggest an anxiolytic activity for MSSE, which make it a potential natural compound for treatment of anxiety disorders.

Anti-anxiety and Anti-depressant Like Effects of Murraya koenigii in Experimental Models of Anxiety and Depression.

Background:Presence of free radical scavenging activity in Murraya koenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression.Aim:The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety.Materials and Methods:The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA), open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST) and tail suspension (TST) tests as compared to control groups in Swiss albino mice.Results:Murraya koenigii 300 mg/kg, p.o. (MK300) and 400 mg/kg, p.o. (MK400) reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400.Conclusion:Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn’t any anxiolytic effect in the elevated plus maze test.

Involvement of 5-HT1A Receptors in the Anxiolytic-Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System.

Quercitrin is a well-known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic-like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic-like effect at 5 and 10 mg/kg. In the marble-burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic-like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic-like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin-1A (5-hydroxytryptamine-1A (5-HT1A)) receptor antagonist WAY-100635 (3.0 mg/kg, i.p.) but not by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5-HT and dopamine) and their metabolites (5-hydroxy-3-indoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic-like effects of quercitrin might be mediated by 5-HT1A receptors but not by benzodiazepine site of GABAA receptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters.

Are Women Sensitive to the Acute Anxiolytic Effect of Diazepam?

Objective: Several studies have shown the influence of ovarian hormones on the GABAergic system. As women are naturally exposed to monthly fluctuation of these hormones, it is possible that their response to benzodiazepines also change over the ovarian cycle. Bearing this in mind, this study aimed to evaluate the possible influence of the ovarian cycle of healthy women on the acute effect of diazepam. Methods: Forty subjectively healthy women were selected and randomly allocated to two different groups, according to their ovarian cycle phase, follicular (6 to 10 days from the first day of the cycle) or luteal (5 to 10 days after detection of urinary LH peak). Both groups completed the Video-Monitored Stroop Color-Word Test (VMSCWT), an experimental model of anxiety, under the influence of diazepam (10 mg) or placebo. Psychological parameters (State-Trait Anxiety Inventory, Self-evaluation of Tension Level, Visual Analogue Mood Scale) and physiological parameters (heart rate and gastrocnemius electromyogram activity) were evaluated throughout the test. All the data obtained were analyzed using analysis of variance (ANOVA) followed by Tukey’s test for post hoc comparisons, both at the 5% significance level. Results: The results showed that, in the follicular phase, women did not respond to the anxiolytic action of diazepam, although a sedative effect was observed; while in the luteal phase, there was no response to either sedative or anxiolytic actions. As a control for the experimental conditions, a group of 18 men was also administered to the VMSCWT. The results confirmed that both the anxiogenic test and the administered drug were working as expected, since diazepam managed to prevent the anxiety induced by the test. Conclusion: Therefore, the present findings indicate that the ovarian cycle can alter the effects of the acute administration of diazepam, which can vary from no effect to sedation, without going through anxiolysis.

Experimental Models of Anxiety for Drug Discovery and Brain Research.

Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright light, or social confrontation), these phenotypes have clear utility in testing the effects of psychotropic drugs. Of specific interest is the extent to which mouse models can be used for the screening of new anxiolytic drugs and verification of their possible applications in humans. To address this problem, the present chapter will review different experimental models of mouse anxiety and discuss their utility for testing anxiolytic and anxiogenic drugs. Detailed protocols will be provided for these paradigms, and possible confounds will be addressed accordingly.

Anxiolytic-like effect of hydroalcoholic extract of ripe pistachio hulls in adult female Wistar rats and its possible mechanisms.

The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications.