Experimental Models Of Anxiety Research Articles

Effect of Lemongrass Aroma on Experimental Anxiety in Humans.

The objective of this study was to evaluate the potential anxiolytic effect of lemongrass (Cymbopogon citratus) aroma in healthy volunteers submitted to an anxiogenic situation. Forty male volunteers were allocated to four different groups for the inhalation of lemongrass essential oil (test aroma: three or six drops), tea tree essential oil (control aroma: three drops), or distilled water (nonaromatic control: three drops). Immediately after inhalation, each volunteer was submitted to an experimental model of anxiety, the video-monitored version of the Stroop Color-Word Test (SCWT). Psychologic parameters (state anxiety, subjective tension, tranquilization, and sedation) and physiologic parameters (heart rate and gastrocnemius electromyogram activity) were evaluated before the inhalation period and before, during, and after the SCWT. Individuals exposed to the test aroma (three and six drops), unlike the control groups, presented a reduction in state anxiety and subjective tension, immediately after treatment administration. In addition, although they presented an anxious response to the task, they completely recovered from it in 5 min, unlike the control groups. Physiologic alterations along the test were not prevented by any treatment, in the same way as has previously been observed for diazepam. Although more investigations are necessary to clarify the clinical relevance of lemongrass essential oil as an anxiety treatment, this work shows that very brief exposure to this aroma has some perceived anxiolytic effects.

S.02.03 Combinatorial pharmacogenomics provides clinical validity and utility for treating major depression

There is a need to improve current treatments for anxiety through developing valid experimental human models of anxiety that allow us to more effectively evaluate novel pharmacological and psychological treatments (and mechanisms of action) in healthy volunteers, prior to evaluation in patient populations. Inhalation of air ‘enriched’ with 7.5% carbon dioxide (CO2) increases selfreport anxiety (worry, tension) and autonomic arousal (heart rate, blood pressure) and provides a novel experimental model of anxiety in healthy humans. Recent evidence from quantitative and qualitative methods suggests that 7.5% CO2 challenge can reliably model core symptoms of anxiety in healthy individuals, including dysfunction in neuropsychological mechanisms that characterise trait anxiety e.g. uncontrollable worry, poor attention control, hyper-vigilance and selective processing of environmental threat. Importantly, the comparable effects of CO2 challenge (in low anxious individuals) and trait anxiety on cognition and emotion processing appear to be independent of elevated state anxiety. Consequently CO2 inhalation may directly challenge neuropsychological mechanisms that characterise generalized trait anxiety rather than transient state anxiety. The model converges with other experimental human anxiety paradigms (e.g. social stress tests and worry induction), but importantly can readily translate into animal paradigms to identify cross-species neural mechanisms that mediate anxious responding. I will summarise evidence from on-going work that is using the CO2 model to evaluate a range of treatment interventions and modalities for anxiety. These include established and potential anxiolytic pharmacological drug treatments, psychological interventions (e.g. cognitive-behavioural attention training), and medical devices that can target prefrontal cortical mechanisms (e.g. trans-cranial direct current stimulation).

Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models in rodents

Scoparia dulcis belonging to the family Scrophulariaceae is an valuable medicinal herb, had showed antiviral, antimalarial, anticancer and antidiabetic activities. The present study was aimed to investigate the anti-anxiety activity of crude ethanolic extract of S.dulcis L by various behavioural models. Preliminary phytochemical investigation revealed the presence of phenols and flavonoids. The extract at 100mg/kg and 200mg/kg was evaluated for anti anxiety activity by Open-field test [OFT], Elevated plus-maze test [EPM], Elevated Zero-maze test [EZM],, Social interaction test [SI] And Novelty induced suppressed feeling latency test [FL] and the results of behavioral tests indicated the dose dependent anti-anxiety activity of Scoparia dulcis which is comparable to standard. It was concluded that crude ethanolic extract showed anti anxiety activity.Further studies are needed to identify the anxiolytic mechanism(s) and the phytochemicals responsible for the observed anxiolytic effect of the hydroalcoholic extract of Scoparia dulcis.

Evaluating psychological interventions in a novel experimental human model of anxiety

Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and provides a novel experimental model of anxiety with which to evaluate pharmacological and psychological treatments for anxiety. To date several psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated using the 7.5% CO2 model; however, it has yet to be used to evaluate psychological interventions. We compared the effects of two core psychological components of mindfulness-meditation (open monitoring and focused attention) against general relaxation, on subjective, autonomic and neuropsychological outcomes in the 7.5% CO2 experimental model.32 healthy screened adults were randomized to complete 10 min of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge participants completed an eye-tracking measure of attention control and selective attention. Measures of subjective anxiety, blood pressure and heart rate were taken at baseline and immediately following intervention and CO2-challenge.OM and FA practice reduced subjective feelings of anxiety during 20-min inhalation of 7.5% CO2 compared to relaxation control. OM practice produced a strong anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA effects occurred in the absence of group differences in autonomic arousal and eye-movement measures of attention.Our findings are consistent with neuropsychological models of mindfulness-meditation that propose OM and FA activate prefrontal mechanisms that support emotion regulation during periods of anxiety and physiological hyper-arousal. Our findings complement those from pharmacological treatment studies, further supporting the use of CO2 challenge to evaluate future therapeutic interventions for anxiety.

Effect of a combination of duloxetine with hydroxyzine on experimental models of anxiety in mice.

Objective:There is a strong association between depression and anxiety. Duloxetine, an antidepressant agent, is also used in the treatment of anxiety. Hydroxyzine is preferred over benzodiazepines in the treatment of anxiety. Present study was designed to study the impact of a combination of duloxetine with hydroxyzine in treatment of anxiety.Materials and Methods:Mice received intraperitoneal injection of normal saline (10 ml/kg), duloxetine alone (10 mg/kg), hydroxyzine alone (10 mg/kg), and hydroxyzine plus duloxetine (5 mg/kg, each).Results:The in vivo results (elevated plus maze and light/dark transition tests) showed significant anxiolytic activity with the hydroxyzine treatment than the control group. The brain monoamines were significantly increased in hippocampi, cerebral cortices, and whole brain in drug-treated groups than in the control group. The group receiving the combination showed similar results in the in vivo models and in vitro tests (brain monoamine estimations) than respective monotherapies, with the exception of a greater increase of norepinephrine levels in cerebral cortices in duloxetine-treated group.Conclusion:Combination of duloxetine with hydroxyzine is not beneficial in anxiolytic treatment than the respective monotherapies. There is a need to study the pharmacokinetic drug-drug interactions to understand the present study outcomes.

GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice

The present study investigated the anxiolytic-like effects of spinosin, one of the major flavonoids in Ziziphi Spinosae Semen (ZSS), in experimental models of anxiety compared with a known anxiolytic, diazepam. Repeated treatment with spinosin (2.5 and 5mg/kg/day, p.o.) significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze compared with the control group. In the light/dark box test, spinosin exerted an anxiolytic-like effect at 5mg/kg. In the open-field test, 5mg/kg spinosin increased the number of central entries. Spinosin did not affect spontaneous activity. The anxiolytic-like effects of spinosin in the elevated plus maze, light/dark box test, and open field test were blocked by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (3mg/kg, i.p.) and 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635 (1mg/kg, i.p.). These results suggest that spinosin exerts anxiolytic-like effects, and its mechanism of action appears to be modulated by GABAA and 5-HT1A receptors.

Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests

Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders. We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats. Female Spraque-Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively. It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them. These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

Evaluation of Anxiolytic-Like Effect of Aqueous Extract ofAsparagusStem in Mice

There are few studies on the neuropharmacological properties of asparagus, which was applied in Chinese traditional medicine as a tonic and heat-clearing agent. The present study was designed to investigate the anxiolytic-like activity of the aqueous extract of asparagus stem (AEAS) using elevated plus maze (EPM) and Vogel conflict tests (VCT) in mice. AEAS significantly increased the percentage of time spent in open arms in EPM, when compared with control group. In the Vogel conflict drinking test, the numbers of punished licks increased to 177% and 174% by the treatment of AEAS at the doses of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight), compared with control group. The serum cortisol level decreased significantly, at the same time. In conclusion, these findings indicated that the aqueous extract of asparagus stem exhibited a strong anxiolytic-like effect at dose of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight) in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.

Anxiolytic activity of methanol leaf extract of Achyranthes aspera Linn in mice using experimental models of anxiety

Objective:To study the anxiolytic activity of methanol extract of Achyranthes aspera Linn (Amaranthaceae).Materials and Methods:Male Swiss albino mice were used. Methanolic extract of Achyranthes aspera (MEAA) was administered in the doses of 100, 300 and 600 mg/kg p.o. Hole board (HB), open field (OF), elevated plus maze (EPM) and light/dark exploration (LDE) tests were used for determination of anxiolytic activity.Results:The methanolic extract of Achyranthes aspera significantly increased the number and duration of head poking in HB test. The extract also significantly increased the time spent and the number of entries in open arm in EPM. In LDE test, the extract produced significant increase in time spent and number of crossings and decreased the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearing, assisted rearing and the squares crossed.Conclusion:In the present study, MEAA exhibited anxiolytic activity which might be attributed to its phyto-constituents viz. alkaloid, steroid and triterpenes. Since Achyranthes aspera is ubiquitous and abundantly grown, it could be a fairly economical therapeutic agent for management of anxiety disorders.

Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression

Context: Recent studies reveal the co-occurrence of both anxiety and depressive disorders in many clinical conditions, which has introduced the concept of mixed anxiety and depressive disorders (MADD).Objective: The study evaluated the ethanol leaf extract of Ocimum sanctum (OS) Linn. (Labiatae), a prominent medicinal plant, against both anxiety and depressive disorder, to evaluate its potency in combating MADD.Materials and methods: Swiss albino mice weighing 20–25 g were used. Gross behavior was observed through Digiscan animal activity monitor. Depression was studied through tail suspension test (TST) and forced swim test (FST). Anxiety experiments included light dark test, elevated plus maze test, and holeboard test. Further, rotarod test was also used to study any defects in motor coordination.Discussion and conclusion: OS at 200 mg/kg showed motor-depressant activity as evaluated with locomotor activity and stereotypy measures. OS at 50 mg/kg shortened the immobility time in the TST and FST, respectively, indicating a possible antidepressant activity. Further, a diminution in the anxiety response at a dose of 50 mg/kg, p.o. body weight was also observed against light dark, elevated plus maze, and holeboard tests, which signifies its antianxiety activity. No defects were observed in the motor coordination of the mice in the rotarod test. Thus, the OS extract shows antianxiety and antidepressant properties at the same dose and can be a potential therapeutic agent against mixed anxiety and depressive syndrome.

Anxiolytic activity of Nymphaea alba Linn. in mice as experimental models of anxiety.

Objective:The aim of the present work was to evaluate the anxiolytic effect of an ethanolic extract of Nymphaea alba Linn. in mice.Materials and Methods:The elevated plus maze test (EPMT), light and dark test (L and DT) and open field test (OFT) were used to assess the anxiolytic activity of the ethanolic extract of N. alba Linn. in mice. In addition, aggressive behavior and motor coordination was also assessed by foot shock induced aggression test (FSIAT) and rota rod test (RRT). Diazepam 1 mg/kg served as a standard anxiolytic drug, administered orally.Results:The ethanolic extract of N. alba (100 and 200 mg/kg, p.o.) significantly increased the percentage of time spent and number of entries in open arm in EPMT. In L and DT, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. In FSIAT, N. alba extract attenuated aggressive behavior related to anxiolytic activity, such as number of vocalization, leaps, rearing, biting/attacks and facing each other in paired mice. Furthermore, the extract produced skeletal muscle relaxant effect assessed by RRT.Conclusion:The results of the present study suggest that an ethanolic extract of N. alba may possess anxiolytic activity and provide a scientific evidence for its traditional claim.

Anti-anxiety activity of Coriandrum sativum assessed using different experimental anxiety models

Interest in alternative medicine and plant-derived medications that affect the “mind” is growing. The aim of present study was to explore the anti-anxiety activity of hydroalcoholic extract of Coriandrum sativum (Linn.) using different animal models (elevated plus maze, open field test, light and dark test and social interaction test) of anxiety in mice. Diazepam (0.5 mg/kg) was used as the standard and dose of hydroalcoholic extract of C. sativum fruit (50, 100 and 200 mg/kg) was selected as per OECD guidelines. Results suggested that extract of C. sativum at 100 and 200 mg/kg dose produced anti-anxiety effects almost similar to diazepam, and at 50 mg/kg dose did not produce anti-anxiety activity on any of the paradigm used. Further studies are needed to identify the anxiolytic mechanism(s) and the phytoconstituents responsible for the observed central effects of the hydroalcoholic extract of C. sativum.

Involvement of dorsal raphe nucleus and dorsal periaqueductal gray 5-HT receptors in the modulation of mouse defensive behaviors

Previous findings point to the involvement of the dorsal raphe nucleus (DRN) and dorsal periaqueductal gray (dPAG) serotonergic receptors in the mediation of defensive responses that are associated with specific subtypes of anxiety disorders. These studies have mostly been conducted with rats tested in the elevated T-maze, an experimental model of anxiety that was developed to allow the measurement, in the same animal, of two behaviors mentioned: inhibitory avoidance and one-way escape. Such behavioral responses have been respectively related to generalized anxiety disorder (GAD) and panic disorder (PD). In order to assess the generality of these findings, in the current study we investigated the effects of the injection of 5-HT-related drugs into the DRN and dPAG of another rodent species, mouse, on the mouse defense test battery (MDTB), a test of a range of defensive behaviors to an unconditioned threat, a predator. Male CD-1 mice were tested in the MDTB after intra-DRN administration of the 5-HT 1A receptor antagonist WAY-100635 or after intra-dPAG injection of two serotonergic agonists, the 5-HT 1A receptor agonist 8-OH-DPAT and the 5-HT 2A/2C receptor agonist DOI. Intra-DRN injection of WAY-100635 did not change behavioral responses of mice confronted with a rat in the MDTB. In the dPAG, both 8-OH-DPAT and DOI consistently impaired mouse escape behavior assessed in the MDTB. Intra-dPAG infusion of 8-OH-DPAT also decreased measures of mouse risk assessment in the rat exposure test. In conclusion, the current findings are in partial agreement with previous results obtained with rats tested in the elevated T-maze. Although there is a high level of similarity between the behavioral effects obtained in rats (elevated T-maze) and mice (MDTB and RET) with the infusion of 5-HT agonists into the dPAG, the same is not true regarding the effects of blockade of DRN 5-HT 1A receptors in these rodent species. These data suggest that there may be differences between mice and rats regarding the involvement of the DRN in the mediation of defensive behaviors.

P01-128 Sensitivity of the generalised anxiety disorder inventory (GADI) to detect changes in two experimental models of human anxiety

We developed and validated a new questionnaire for the assessment of the symptom profile and severity of generalised anxiety, the Generalised Anxiety Disorder Inventory (GADI). The 18-item scale (Argyropoulos et al, 2007, J Psychopharmacology, 21: 145-152) showed good reliability, convergent and divergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It distinguishes accurately GAD patients from non-patient controls. The cognitive factor also distinguishes GAD from other anxiety disorders and depression. The sensitivity of the GADI to detect changes in symptom levels was tested in two experimental models of anxiety induction; the inhalation of 7.5% CO2 over a period of 20 minutes, which models generalised anxiety, and a single vital capacity inhalation of 35% CO2, which models panic anxiety (Bailey et al, 2005, Depression & Anxiety, 21: 18-25; Bailey et al, 2007, J Psychopharmacology, 21: 42-49). We found that the GADI was able to detect the differential drug effect of a benzodiazepine (alprazolam) and placebo in the anxiety induced by these tests in healthy volunteers.

Anxiolytic activity of Vitex negundo Linn. in experimental models of anxiety in mice.

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from the roots of Vitex negundo (VN) using the elevated plus maze (EPM) and light–dark exploration test in mice. Male mice were either treated orally with the VN extract or the positive control diazepam, respectively, 1 hour before behavioral evaluation. Oral administration of 100 and 200 mg/kg of VN extract significantly (P > 0.01) increased the percentage time spent on and the number of entries into the open arms of the EPM. The effect was comparable to that of the benzodiazepine diazepam (2 mg/kg p.o.). In light–dark exploration test, diazepam-treated rats significantly increased the time spent in light arena and decreased the duration of immobility, while VN treated rats also showed a significant (P >0.01) increase in the time spent (100 and 200 mg/kg) in light arena. Diazepam and the VN extracts do not produced any overt motor dysfunction. These results indicate that VN is an effective anxiolytic agent. In conclusion, the action of extract upon the anxiety models tested are in accord with the traditional use of VN L. and could be useful in primary medical care. Key words: Vitex negundo, anxiolytic, elevated plus maze, light–dark exploration, locomotor activity

Models and mechanisms of anxiety: evidence from startle studies

Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). The objectives of the study are to (1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, (2) describe experimental models of anxiety, as opposed to fear, in humans, (3) examine the relevance of these models to clinical anxiety. The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

Anxiolytic-like effects of oleamide in group-housed and socially isolated mice

Oleamide ( cis-9,10-octadecenoamide) is an endogenous sleep-inducing lipid and prototypic member of a new class of biological signaling molecules identified in recent years. In the present study, the anxiolytic-like effect of oleamide was studied in several experimental models of anxiety in group-housed and socially isolated mice. As the results show, socially isolated mice exhibited an anxiogenic-like profile in the elevated plus-maze test, the light/dark test, and the hole-board test, which could be significantly reversed by oleamide (10 or 20 mg/kg, i.p.). Moreover, oleamide significantly reduced the anxiety levels in grouped-housed mice. In the isolation-induced aggressive test, oleamide markedly reduced the attacking duration and increased the attacking latency. It is concluded that oleamide has an anxiolytic-like effect in socially isolated or group-housed mice, which suggests that fatty acid amides might be involved in the regulation of anxiety-related behavior in mice.

P.2.29 Involvement of NK2 receptors in experimental models of anxiety and depression under basal and stress-related conditions

SR 48968, a non-peptide tachykinin NK2 receptor antagonist, has been shown to possess sub-micromolar affinity for NK3 receptors present in the guinea pig. In the present study, we have compared the binding affinities of SR 48968 to the cloned human and rat NK3 receptors expressed in CHO cells. Using [125I]-[MePhe7]-neurokinin B as the radioligand, SR48968 displayed an IC50 value of 350 nM for the human NK3 receptor as compared with a value of greater than 10 μM for the rat NK3 receptor. Exposure of cells transfected with human NK3 receptor cDNA to [Pro7]-neurokinin B increased inositol phospholipid turnover in a concentration-dependent manner and this response was blocked competitively by SR 48968. Our results demonstrate that SR 48968 is an antagonist at the human NK3 receptor and may be a useful tool for elucidating the species-dependent variations in the non-peptide antagonist binding site(s) on the NK3 receptor.

Effects of the essential oil from Citrus aurantium L. in experimental anxiety models in mice

Citrus aurantium L. is popularly used to treat anxiety, among other indications suggesting central nervous system action. Previous studies showed anxiolytic effect in the essential oil from peel in mice evaluated on the elevated plus maze [Carvalho-Freitas, M.I.R., Costa, M., 2002. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biological and Pharmaceutical Bulletin 25, 1629–1633.]. In order to better characterize the activity of the essential oil, it was evaluated in two other experimental models: the light–dark box and the marble-burying test, respectively related to generalized anxiety disorder and to obsessive compulsive disorder. Mice were treated acutely by oral route 30 min (single dose) or once a day for 15 days (repeated doses) before experimental procedures. In light–dark box test, single treatment with essential oil augmented the time spent by mice in the light chamber and the number of transitions between the two compartments. There were no observed alterations in the parameters evaluated in light–dark box after repeated treatment. Otherwise, single and repeated treatments with essential oil were able to suppress marble-burying behavior. At effective doses in the behavioral tests, mice showed no impairment on rotarod procedure after both single and repeated treatments with essential oil, denoting absence of motor deficit. Results observed in marble-burying test, related to obsessive compulsive disorder, appear more consistent than those observed in light–dark box.

Behavioral effects of sinomenine in murine models of anxiety

The present study was designed to investigate the putative anxiolytic-like effect of sinomenine in three experimental models of anxiety in male rats and mice. Use of the elevated plus-maze test revealed that sinomenine (20 and 40 mg/kg, p.o.) increased the percentage of open arm entries and diazepam (2 mg/kg, p.o.) increased the percentage of open arm entries, the percentage of time spent on open arms and total arm entries in mice. In the light/dark transition test, sinomenine (20 and 40 mg/kg, p.o.) increased time spent in the light area and diazepam (2 mg/kg, p.o.) increased time spent in the light area and the overall movements in mice. In the social interaction test, the sinomenine-treated animals significantly increased social interaction time in low light unfamiliar (7 mg/kg, p.o.) and high light unfamiliar conditions (7 and 14 mg/kg, p.o.) as well as diazepam (3 mg/kg, p.o.). Sinomenine (28 mg/kg, p.o.) can also decrease squares entered in rats in social interaction test under low light unfamiliar condition. In the open-field test, sinomenine (160 mg/kg) decreased squares entered in mice. Thus, these findings indicated that sinomenine exhibited anxiolytic-like effect.