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.
Herbal based remedies are used worldwide to treat psychiatric disorders. The aim of this study was to analyse the essential oil composition of Achillea Wilhemsii C. Koch (Asteraceae) and to evaluate its anxiolytic effects in the elevated plus maze (EPM) model of anxiety in rat. Gas chromatography/mass spectrometry (GC/MS) analysis of the essential oil showed that the main compounds of the oil were p-ocimen (23%), 1, 8-cineole (20.8%) and carvone (19.13%). The EPM results showed that 1 mg/kg (i.p.) of the oil significantly (P<0.05) increased the percentage of the time spent and the number of entries in the open arms of the maze while it did not change the total number of entries in the maze arms. These effects were not reversed with 2 mg/kg flumazenil and 5 mg/kg naloxone. We concluded that a minimum dose of 1 mg/kg of the oil has anxiolytic effects which are not probably mediated through GABA and opioid receptors.
Achillea Wilhelmsii C. Koch; Anxiolytic; Essential oil; GC/MS; Elevated plus maze
The elevated plus-maze (EPM) test is one of the most commonly used behavioral assays to evaluate anxiety-related behavior in rodents. It is an economic test (5 min duration) without prior conditioning of the animals. The critical measure for anxiety is the time spent in the open arms of the maze. A confounding problem of the EPM is the so called one-trial tolerance (OTT), characterized by a marked decrease of open arm exploration in spite of treatment with anxiolytic acting benzodiazepines upon re-exposure to the EPM. This consistent finding is often raised as an evidence for the inappropriateness to re-test rodents in the EPM. However, a reliable re-test paradigm would broaden the usability and effectiveness of this test. Therefore, we tested how an extension of the inter-trial interval to 28 days (instead of the usual 24 h), and an additional change of the testing room would affect the open arm time and other behaviors on the EPM. In two experiments, drug-naive Wistar rats were exposed to the EPM on trial 1, and treated intraperitoneally with either vehicle or midazolam (0.25 mg/kg) 30 min before trial 2. Then, trial 2 (28 days after trial 1) was carried out in either the same testing room (Experiment 1) or in another unfamiliar room (Experiment 2). Twenty-eight days after trial 1 the open arm time of the rats in the vehicle treated control rats of both experimental groups was comparable to that of the first trial, independent of the testing room. Most importantly, we found that the treatment with the benzodiazepine midazolam had a significantly anxiolytic-like (i.e., increase of open arm time) effect in trial 2 only when conducted in the previously unfamiliar testing room (Experiment 2). We suggest that in order to reliably re-test the EPM and to prevent confounding effects due to the OTT, an inter-trial interval of 28 days and a change in testing rooms reinstates anxiolytic-like actions of benzodiazepines.
re-test EPM; one-trial tolerance; midazolam; motivation; memory
Olive oil is the major component of the Mediterranean diet and has rich history of nutritional and medicinal uses. In the present study, the antidepressant and anxiolytic effects and their neurochemical basis following repeated administration of extravirgin olive oil were monitored. Male albino Wistar rats were used during study. Animals of test group were given olive oil orally at the dose of 0.25 mL/kg daily for 4 weeks. Control rats received equal volume of water. Elevated-plus maze (EPM) test and forced swim test (FST) were performed for the assessment of anxiety and depression like symptoms. An increase in time spent in open arm in EPM and increased struggling time in FST following long-term administration of olive oil indicate that olive oil has anxiolytic and antidepressant properties. Neurochemical results showed that repeated administration of olive oil decreased the levels of brain 5-HT (5-hydroxytryptamine), 5-HIAA (5-hydroxyindoleacetic acid), and levels of DA (dopamine); however, levels of DA metabolite HVA (homovalinic acid) were increased. Hence, present findings suggest that olive oil has neuroprotective effects. It reduces behavioral deficits via altering 5-HT and DA metabolism. So it could be used as a therapeutic substance for the treatment of depression and anxiety.
In human beings, susceptibility to anxiety disorders can be relatively high during adolescence. Understanding the ontogeny of anxiety-like behavior in laboratory rodents has implications for developing anxiolytic drugs that are suitable for this age group. Given the dearth of information about adolescent rodents, this study examined the response of both male and female adolescent, late adolescent, young adult, and older adult rats to three tests of anxiety-like behavior: the emergence test (ET), open field (OF), and elevated plus-maze (EPM). The results showed that adolescent rats exhibited a higher anxiety-like response than adults on each test; the amount of locomotion in the OF and percentage of time spent on the open arms of the EPM increased across the age groups, while older adult rats made the fewest start box re-entries in the ET. These results support the hypothesis that adolescent rats have a more pronounced response to stressors than do adults. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 731–739, 2010.
adolescence; anxiety; rats; open field; elevated plus-maze; sex differences
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.
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.
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.
Achyranthesaspera; anxiolytic activity; elevated plus maze; hole board; light/dark exploration; MEAA; open field
The aim of the present study was to evaluate the anxiolytic effects of hydroalcoholic extract (HE) of Nepeta persica Boiss. (Lamiaceae) on the elevated plus-maze (EPM) model of anxiety. The extract of arial parts of the plant was administered intraperitoneally to male NMRI mice, at various doses, 30 min before behavioural evaluation. The HE extract of N. persica at the dose of 50 mg kg−1 significantly increased the percentage of time spent and percentage of arm entries in the open arms of the EPM. This dose of plant extract affected neither animal's locomotor activity nor ketamine-induced sleeping time. The 50 mg kg−1 dose of the plant extract seemed to be the optimal dose in producing the anxiolytic effects, lower or higher doses of the plant produce either sedative or stimulant effects. At 100 mg kg−1, the plant extract increased the locomotor activity. These results suggested that the extract of N. persica at dose of 50 mg kg−1 possess anxiolytic effect with less sedative and hypnotic effects than that of diazepam and causes a non-specific stimulation at 100 mg kg−1.
anxiety; elevated plus-maze; Nepeta persica; sedative
There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP), known as “Valeriana del monte”, and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM), forced swimming (FST), strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5%) and time spent (44.7%) in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.
The aim of the present study is to demonstrate the anxiolytic and anticonvulsant effects of a hydroalcoholic extract obtained from the aerial parts of Cissus sicyoides L. (CS) (Vitaceae) on male and female mice using several behavioral assays. Groups of males and females treated via intraperitoneal (IP) with doses of 300, 600, and 1000 mg/kg of the extract showed significant action in the elevated plus-maze (EPM), time spent in the open arms, and number of entries in the open arms. The board-hole test also showed a significant increase in the time spent in head-dipping and in marble-burying test of the number of marbles buried. The same treatment increased the duration of sleeping time induced by sodium pentobarbital and also showed a significant increase in protection against pentylenotetrazole-induced convulsions. These results indicate an anxiolytic and anticonvulsant-like action from C. sicyoides L. extract on mice, probably due to the action of flavonoid(s), Linalool, and α-tocopherol present in the C. sicyoides leaves.
The cholinergic nervous system and acetylcholine esterase are involved in chronic intoxication with organophosphorous insecticides. The present study aims to investigate the influence of the chronic toxicity of these chemicals on behaviors related to anxiety, using the elevated plus maze (EPM), in the male adult mouse.
Material and methods
Either water or 1% concentration of malathion was applied dermally to the male adult mice (10 s, once daily for 28 days) and, on day 29, the EPM test was done.
Time spent in the open arms (TSOA) in intoxicated animals was decreased by over 50% compared to the controls (p = 0.047). In contrast, time spent in closed arms was significantly higher in the malathion-exposed mice (p = 0.025). Percentage of open arm entries (OAE) was slightly smaller in the malathion-treated group in comparison to the control animals. Percentage of closed arm entries (CAE) in the treated group was slightly higher than the value in the control animals.
The results showed that chronic toxicity of malathion may lead to an anxiety-like behavior in the animal model used in this study. It is difficult to extend these findings to clinical situations. However, more experimental work in different animal species as well as epidemiological studies in human subjects in this regard are highly recommended.
anxiety; elevated plus maze; malathion; mouse; organophosphates
The present study was undertaken to evaluate the anxiolytic and anti-depressant activity of Sarasvata choorna. The anxiolytic activity was evaluated in elevated plus maze (EPM) and the anti-depressant activity was evaluated in forced swimming test (FST). The efficacy of Sarasvata choorna was compared with the standard anti-anxiety (diazepam 2 mg/kg) and anti-depressant (imipramine – 5 mg/kg) drugs. It was observed that Sarasvata choorna at the dose of 390 mg/kg is as effective as standard drugs used in anti-anxiety and anti-depressant activities in mice by increasing time spent in open arm and entries to open arm in EPM model and increasing immobility time in FST model respectively. Hence it can be concluded that Sarasvata choorna may be used as a potent therapeutic agent in treating anxiety and depressive disorders.
Anxiolytic; anti-depressant; elevated plus maze; imipramine; Sarasvata choorna
Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.
Anxiety; Tyrosine hydroxylase; Substantia nigra; Hypoxia-ischemia
Chrysanthemum indicum Linne is an ancient herbal medicine used to treat bone and muscle deterioration, ocular infl ammation, headache, and anxiety in Korea, China, and Japan. Furthermore, tea derived from Chrysanthemum indicum Linne has been used to treat anxiety by facilitating relaxation and curing insomnia. However, no reports exist on the anxiolytic-like effects of Chrysanthemum indicum Linne water extract (CWE) in mice. In the present study, we investigated the anxiolytic-like effects of CWE using the elevated plus-maze (EPM) test in mice. CWE, at a dose of 500 mg/kg (p.o.), signifi cantly increased the time spent in the open arms of the EPM compared to a vehicle-injected control group. Moreover, the effect of CWE (500 mg/kg) was blocked by bicuculline (a selective GABAA receptor antagonist) and WAY 100635 (a selective 5-HT1A receptor antagonist). Taken together, these fi ndings suggest that the anxiolytic-like effects of CWE might be mediated by the GABAA receptor and the 5-HT1A receptor.
Chrysanthemum indicum Linne; Anxiolytic-like effects; Elevated plus maze; GABAA receptor; 5-HT1A receptor
The aim of this study was to study the ameliorative effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression.
Materials and Methods:
The study was carried out using male albino rats (200 ± 50 g). The effect of O. sanctum and C. sinensis was evaluated for anxiety and depression using elevated plus maze (EPM) test, open field test (OFT), forced swim test (FST), and tail suspension test (TST).
Restraint stress (3 h/day for six consecutive days) induced a significant reduction in both the percentage number of entries and time spent in open arms in EPM, and these changes were reversed with post-treatment of aqueous extract of O. sanctum and C. sinensis (100 mg/kg for 6 days). Restraint stress-induced (a) increased latency and (b) decreased ambulation and rearing were also reversed by O. sanctum and C. sinensis in OFT. A significant increase in immobility period was observed in FST and TST after restraint stress. O. sanctum and C. sinensis significantly reduced the immobility times of rats in FST and TST.
O. sanctum and C. sinensis possess anxiolytic and antidepressant activities.
Anxiety; Camellia sinensis; depression; Ocimum sanctum; restraint stress
To analyse the behavioral effects of Melissa officinalis extract in rats following acute or subacute treatment.
Materials and Methods:
The behavioral effects of an acute or subacute (10-day course) orally administered M. officinalis (MO; 0, 30, 100 or 300 mg/kg) ethanol extract were evaluated in male and female Wistar rats in elevated plus-maze (EPM), forced swimming (FS) and open field (OF) tests. The effects of diazepam (DZP; 1 mg/kg) and fluoxetine (FXT; 10 mg/kg) were also assessed.
In the EPM test, the percentage of open arm entries and open arm times of both males and females given the subacute M. officinalis ethanol extract were significantly higher than those of the vehicle-treated animals but were at levels similar to those observed in the DZP group, regardless of the treatment length. In the FS test, immobility duration was significantly lower in both males and females treated with the plant extract when compared to vehicle-treated counterparts. A 10-day treatment with FXT induced the same antidepressant response, regardless of gender, and was more effective than the M. officinalis extract. Male and female rats demonstrated distinct gender profiles, and treatment × gender interactions were observed. Locomotion in the EPM and OF tests was not significantly altered by treatments.
The potential psychoactive properties of M. officinalis may provide a unique pharmacological alternative for certain psychiatric disorders; however, the efficacy appears to be dependent on both gender and administration length.
Anxiety; depression; gender; locomotion; Melissa officinalis
Aim and Objectives:
To evaluate anxiolytic effect of stem bark ethanol and chloroform extracts of Erythrina mysorensis in mice.
Materials and Methods:
The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), and motor coordination by rotarod test (RRT). Twenty four Swiss albino male mice were divided into four groups of six mice each. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received ethanolic and chloroform extract of Erythrina mysorensis, 200 and 400 mg/kg p.o., respectively.
Mice treated with diazepam (1 mg/kg, p.o.) showed significant (P < 0.001) increase ini the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (P < 0.05) decreased. Oral administration of chloroform and ethanol extract of E. mysorensis exhibited significant (P < 0.05) increase in the number of open arm entries and time spent with significant (P < 0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. Chloroform and ethanol extracts treated mice also produced significant increase in the number of rearings (P < 0.05), assisted rearings and number of squares crossed (P < 0.01). Rotarod test showed significant (P < 0.01) reduction in motor activity at 45 min with diazepam and E. mysorensis extracts (400 mg/kg) as compared to groups 3 and 1.
Erythrina mysorensis possess significant anxiolytic activity in the mice. It can be a promising anxiolytic agent.
Elevated plus maze test; Erythrina mysorensis; open field test; Rotarod test
Changes in levels of estradiol and progesterone that occur with the transition to reproductive senescence may influence nociception or affect.
To ascertain whether nociceptive and affective processes change with reproductive senescence, this study examined pain and anxiety-like behaviors in middle-aged female rats that were reproductively competent, transitioning to reproductive senescence, or reproductively senescent.
Middle-aged (12–14 months old) female rats (N = 46) were tested in the following tasks to assess pain and anxiety-like behavior: tail flick, elevated plus maze, elevated zero maze, mirror maze, Vogel punished drinking, and defensive burying. For the tail-flick task, the latency for rats to move their tail from a heat source, as an indication of pain sensitivity, was determined. In the elevated plus and elevated zero mazes, the time spent on the open arms or quadrants, respectively, were determined as measures of reduced anxiety behavior. In the mirror maze, the time spent in the mirrored portion of the chamber was used as an indicator of anxiety-like responding. In the Vogel task, the number of punished licks made was determined as a measure of reduced anxiety-like behavior. In the defensive burying task, the duration spent by rats burying an electrified prod postfootshock was utilized as an index of anxiety-like responding. All rats were experimentally naive, retired breeders from our colony and had not had a litter or been lactating for 1 to 4 weeks before behavioral testing.
Although tail-flick latencies were not significantly different among rats that were reproductively competent or senescent, reproductively competent rats had less anxiety-like behavior in the elevated plus maze (more time spent on the open arms: F2,43 = 5.93; P < 0.01), elevated zero maze (more time spent on the open quadrants: F2,43 = 4.62; P = 0.01), and Vogel punished drinking task (more punished licks made: F2,43 = 3.76; P = 0.03). There were no statistically significant differences in the mirror maze and defensive burying task.
In this study of adult female rats, nociceptive behavior did not vary significantly with reproductive senescence, but anxiety-like behavior of rats did.
estrogen; progesterone; anxiety; affect; aging; menopause
Discontinuation of drug intake in cocaine abusers commonly produces a variety of adverse withdrawal symptoms among which anxiety and depression-related behavior are prevailing during the initial period of abstinence. The aim of this study was to provide further insight into the neurobiological dysregulations that might contribute to these pathological states. Rats were treated with cocaine or saline for 14 days (20 mg/kg; i.p) and anxiety-related behavior was assessed in different paradigms (elevated plus-maze (EPM), confinement to an open arm of the EPM and shock-probe burying tests) for up to 4 weeks after withdrawal. Depression-like behavior was assessed by the forced swim test and sucrose preference test. Altogether our results demonstrated that cocaine withdrawal induced persistent heightened levels of anxiety that last for at least 28 days but did not affect depression-like behavior. We then used Fos immunohistochemistry to map neuronal activation patterns in withdrawn rats confined to one open arm of an EPM, and a double labeling procedure using Fos immunohistochemistry and in situ hybridization of glutamic acid decarboxylase or vesicular glutamate transporter mRNAs to identify the phenotype of the activated neurons. Our data showed that the exacerbated anxiety observed in cocaine withdrawn rats exposed to an elevated open arm was accompanied by an altered reactivity of the dorsal part of the medial prefrontal cortex (anterior cingulate and dorsal prelimbic cortices), the paraventricular thalamic nucleus and the lateral and anterior areas of the hypothalamus. In the medial prefrontal cortex, we evidenced a negative correlation between Fos expression in its dorsal part and open arm-induced freezing in NaCl-treated rats but not in cocaine withdrawn rats. We also found that more than 65% of activated neurons were glutamatergic projection neurons. The present study provides new insights into the neuroanatomical regions and neuronal cell types that may underlie pathological anxiety during cocaine withdrawal.
Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known for its medicinal properties. This study aimed to understand the mechanism of Lactuca sativa extract with respect to pharmacological action.We investigated the anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on mice. The behavioral tests performed on mice models to assess anti-anxiety properties were: open field test (OFT), elevated plus maze test (EPM), elevated T maze test, and marble burying test. Increased locomotor activity and time spent in the “open-arm” were observed in extract fed group. Malondialdehyde (MDA) and nitrite levels were decreased, catalase and glutathione levels were increased in Lactuca sativa treated mice. The data obtained in the present study suggests that the extract of Lactuca sativa can afford significant protection against anxiolytic activity.
Lactuca sativa; anxiety; nitrite; open field test (OFT); elevated plus maze test (EPM); malondialdehyde (MDA)
The present study examined the anxiolytic and antidepressant effects of the aqueous extract of Alafia multiflora Stapf (AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol a β-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce significantly the immobility time and increase swimming as well as climbing duration. Taken together, the present work evidenced anxiolytic effects of the aqueous extract of AM that might involve an action on benzodiazepine-type receptors and an antidepressant effect where noradrenergic mechanisms will probably play a role.
Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.
Compound Valeriana jatamansi Jones is a formula for treating anxiety-related diseases in the clinic, which is composed of Valeriana jatamansi Rhizoma et Radix, Ziziphi Spinosae Semen, Albiziae Cortex and Junci Medulla. The purpose of this study was to explore the anxiolytic properties of this compound in mice.
Male ICR mice were treated with compound Valerianae Jatamansi Jones (1.2 g/kg, 2.4 g/kg, 4.8 g/kg), saline, diazepam (2 mg/kg) orally for 10 days and then exposed to elevated maze-plus (EPM) and light–dark box (LDB). The effects of the compound on spontaneous activity were evaluated by locomotor activity test. We further investigated the mechanism of action underlying the anxiolytic-like effect of compound by pre-treating animals with antagonists of benzodiazepine (flumazenil, 3mg/kg) prior to evaluation using EPM and LDB.
Compound Valerianae Jatamansi Jones (2.4, 4.8 g/kg, p.o.) significantly increased entries (P<0.05) into and time spent (P<0.05) on the open arms of the EPM, and number of transitions (P<0.05) and time spent (P<0.05) in the light compartment of the LDB. However, the anxiolytic-like effects of compound were significantly reduced by pre-treatment with flumazenil (P>0.05). In addition, compound Valerianae Jatamansi Jones treatment didn’t affect the spontaneous activity in mice (P> 0.05).
The present study supports the hypothesis that compound Valeriana jatamansi Jones exert anxiolytic action but no sedative effects in mice and that this effect might be mediated by benzodiazepine receptors.
Compound Valeriana jatamansi Jones; Anxiolytic; Elevated maze-plus; Light–dark box; Benzodiazepine receptors
To investigate the anti-anxiety activity of “6k”, a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice.
Materials and Methods:
Anti-anxiety activity of “6k” (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). Diazepam (2 mg/kg, i.p.) served as reference standard.
“6k” significantly (P < 0.05) increased the time and entries in open arm in EPM as compared to vehicle control group. Further, “6k” significantly (P < 0.05) increased the central and peripheral ambulation along with rearings and time in central area; whereas, reduced the fecal pellets in OFT as compared to vehicle control group. There was significant (P < 0.05) reduction in the latency to enter dark chamber; whereas, increased number of crossings and time in light chamber in L&D aversion test by treatment with “6k” as compared to vehicle control group. In HBT, “6k” significantly (P < 0.05) increased the number of head dipping and squares crossed; whereas, reduced the latency for first head dip and number of fecal pellets as compared to vehicle control group.
A novel 5-HT3 receptor antagonist has anti-anxiety action.
5-HT3 antagonist; anxiety; elevated plus maze; open field test; hole board test
To investigate the effects of a hydroalcoholic extract of the Sphaeranthus indicus (SIE) against experimentally induced anxiety, depression and convulsions in rodents. The SIE (100, 200, 500 mg/kg, p.o.) was used in elevated plus maze, open field, forced swimming, and tail suspension tests in mice. The same doses were also used to evaluate its anticonvulsant effect on pentylenetetrazole (PTZ)-induced convulsions in mice and maximal electroshock (MES)-induced convulsions in rats. SIE was found to increase the number of entries and the time spent in the open arms of the maze at a dose of 100 mg/kg, p.o., indicating its anxiolytic activity. On the other hand, higher doses of SIE (200 and 500 mg/kg, p.o.) decreased open arm entries and time spent in the open arms of the maze in the elevated plus maze test indicating an absence of anxiolytic activity. However, this effect could have been related to a decrease in the locomotor activity of the mice and not to an anxiogenic effect, as indicated by the reduction in the total number of entries in the elevated plus maze. SIE also (at doses of 200 and 500 mg/kg, p.o.) decreased locomotor activity but did not affect emotional activity parameters in the open field test, suggesting a possible central nervous depressant activity. SIE also increased the immobility time in the forced swimming test at an oral dose of 500 mg/kg but did not significantly modify the activity in the tail suspension test. SIE protected rats against MES-induced convulsions and mice against PTZ-induced convulsions. Sphaeranthus indicus demonstrated anxiolytic, central nervous depressant, and anticonvulsant activities in rodents, thus supporting the folk medicinal use of this plant in nervous disorders.
Elevated plus maze test; forced swim test; maximal electroshock-induced convulsions; open field test; pentylenetetrazole-induced convulsions; Sphaeranthus indicus
Circadian dysregulation in sleep pattern, mood, and hypothalamic-pituitary-adrenal (HPA) axis activity, often occurring in a sexually dimorphic manner, are characteristics of depression. However, the inter-relationships among circadian phase, HPA function, and depressive-like behaviors are not well understood. We investigated behavioral and neuroendocrine correlates of depressive/anxiety-like responses during diurnal (‘light’) and nocturnal (‘dark’) phases of the circadian rhythm in the open field (OF), elevated plus maze (EPM), forced swim (FST), and sucrose contrast (SC) tests. Plasma corticosterone (CORT) was measured after a) acute restraint and OF testing and b) FST. Both phase and sex significantly influenced behavioral responses to stress. Males were more anxious than females on the EPM in the light but not the dark phase. Further, the open:closed arm ratio was lower in the dark for females, but not males. By contrast, in the FST, females showed more “despair” (immobility) when tested in the dark, while phase did not affect males. Acute restraint stress increased OF activity in the light, but not the dark, phase. CORT levels were increased in both sexes following the FST, and in males and light phase females post-OF. As expected, females had higher CORT levels than males, even at rest, and this effect was more pronounced in the Dark phase. Together, our data highlight the sexually dimorphic influences of circadian phase and stress on behavioral and hormonal responsiveness.
open field; elevated plus maze; sucrose contrast; Porsolt forced swim; HPA axis; circadian phase; diurnal variation; corticosterone; depression; anxiety; rat