Number Of Open Arm Entries Research Articles

Anxiolytic-like effect of hydrogen sulfide (H2S) in rats exposed and re-exposed to the elevated plus-maze and open field tests

Hydrogen sulfide (H2S), an endogenous gaseous mediator, modulates many physiological functions in mammals but evidence of its involvement in emotional and behavioral aspects is currently scarce. We hypothesized that this gas plays a modulatory role in behavioral parameters in rats submitted to tests (for 5min) in the open field (OF) and elevated plus-maze (EPM – test and retest). Male Wistar rats (200–250g) were intraperitoneally injected with saline or Na2S (a H2S donor; 4, 8 and 12mg/kg) either once or for 8days, and submitted to the OF test or to the EPM test and retest. A third group (naïve) was not injected but exposed to the same experimental protocols. In the OF test, Na2S injected for 8days caused a decrease in self-cleaning (4, 8 and 12mg/kg) and freezing behaviors (8 and 12mg/kg), and a rise in the rate of line crossings in the central part of the arena (12mg/kg). In the EPM test and retest, Na2S at 12mg/kg for 8days caused an increase in the number of open arm entries and in the percentage of time spent on open arms. Our data are consistent with the notion that H2S exerts anxiolytic-like effects in rats submitted to the EPM and OF tests. Moreover, this gaseous modulator reduces aversive learning in the EPM retest.

Effects of (−)-Sesamin on Chronic Stress-Induced Anxiety Disorders in Mice

This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6mA, 1s every 5s, 3min). Mice treated with (-)-sesamin (25 and 50mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.

P.1.h.005 - Anxiolytic-like effect of gallic acid and quercetin in young/healthy rats

3,4-Methylenedioxymethamphetamine (MDMA) is a compound structurally similar to methamphetamine, which has become one of the most widely used illicit substances. Animal studies investigating acute effects of MDMA on anxiety are unclear since, although an anxiogenic-like action of MDMA in different animal models of anxiety has been mainly described, there is also evidence supporting an anxiolytic-like effect for this drug. An attempt was made to clarify the possible anxiogenic-like profile of MDMA (1, 8 and 15 mg/kg ip) by analyzing its effect on behavior of male mice in the elevated plus-maze test. Moreover, the possible development of tolerance to the effects of MDMA on anxiety after its subchronic administration for 5 consecutive days was examined. The parameters evaluated included: (1) total time in open arms, (2) total time in closed arms, (3) total time in central area, (4) number of open arm entries, (5) number of closed arm entries and (6) number of central area entries. Acute treatment with MDMA (8 mg/kg) significantly reduced the time spent in the open arms, as well as markedly increasing the number of entries in the closed arms and in the central area, as compared with the control group, suggesting that MDMA, at this dose, has an anxiogenic-like activity. Mice subchronically treated with the drug (1 and 8 mg/kg) displayed a notable reduction in the time spent in the open arms, accompanied by an increase in the time spent in the closed arms and in the central platform. These results indicate that the anxiogenic-like effect found after acute treatment is not only maintained but also more marked after subchronic treatment. In contrast, mice treated subchronically with the highest dose of MDMA (15 mg/kg) exhibited a significant increase in the time spent in the open arms as well as a marked reduction in the time spent in the closed arms, supporting an anxiolytic-like activity of the drug. A possible dual pharmacological property of MDMA on anxiety is suggested.

Behavioral effects of Citrus limon and Punica granatum combinations in rats.

Dietary supplements are becoming more influential as viable treatment for common chronic diseases and to promote normal development and functions of all system including brain. Disorders like anxiety and depression may be managed through healthier variations is dietary pattern, since there are indications that diet rich in antioxidants and vitamins diminish anxiety and depression. Hence this investigation was planned to assess the behavioral effects of Citrus limon and Punica granatum in two combination doses i.e. 0.4+5ml/kg and 0.2+8ml/kg C. limon and P. granatum respectively in rats. Antidepressant and anxiolytic effects were explicitly judged twice during 15days using forced swimming and open field tests and elevated plus maze. In open field test C. limon and P. granatum showed increase in distance travelled, number of central entries and number of rearing's at 0.4+5ml/kg combination, in the elevated plus maze, number of open arm entries were found to be augmented and in forced swimming test, there was decline in duration of immobility and rise in duration of climbing at both combinations i.e. 0.4+5ml/kg and 0.2+8ml/kg C. limon and P. granatum. These results suggest that C. limon and P. granatum at 0.4+5ml/kg combination have anxiolytic and antidepressant effect.

Evaluation of antioxidant effect of Nerium indicum in anxious rats.

Aim:The aim of this study was to analyze the ethyl acetate extract of Nerium indicum (NIE) flower for its antioxidant effect in anxious Sprague–Dawley rats.Materials and Methods:Animals were divided into six groups (n = 6) and treated with 200 mg/kg and 400 mg/kg p.o. of NIE for 21 days to assess its preventive and curative effects. Anxiety was induced by isolating animals socially for 21 days. Elevated plus maze (EPM) and light and dark model were used for measuring anxiety in animals. Oxidative stress parameters such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in blood and brain tissue homogenate were monitored after 21 days of social isolation in animals.Results:Rats were treated with NIE 200 mg/kg and 400 mg/kg p.o. Both the treatments showed a significant (P < 0.001) increase in the number of open arm entries and time spent in open arm in EPM when compared with the negative control. Results also demonstrated that there was a significant (P < 0.001) increase in the number of lightbox entries and time spent in light box in light and dark model when compared with negative control. There was a significant (P < 0.001) improvement in endogenous anti-oxidants such as SOD, CAT, reduced GSH, and decreased levels of LPO in blood and brain tissue when compared with the negative control.Conclusion:The present study suggests the role of NIE in the treatment of anxiety, possibly by modulating the oxidative stress.

Effect of Ellagic Acid on Animal Behavior in Elevated Plus Maze and Open Field Tests

Background: Anxiety is one the most common psychiatric disorders. Recently, anti-oxidants have been shown to possess anxiolytic properties. Objectives: The present study aimed to investigate anxiolytic effect of ellagic acid (EA) in mice and its interaction with GABAA receptor. Materials and Methods: 184 male albino mice (25 - 30 g) were randomly assigned into two subgroups (12 groups in each). In the first set of experiments, to evaluate acute administration of EA (single dose) on anxiety, experimental groups (10 groups, 8 mice per group) were control (received vehicle), EA-treated groups (received ellagic acid, 3, 10, 30 and 100 mg/kg, i.p.), diazepam (DZP)-treated groups (received DZP, 1, 3 and 5 mg/kg, i.p.), Flumazenil (FLZ) + diazepam-treated group (received FLZ, 3 mg/kg and + DPZ, 5 mg/kg, i.p.) and FLZ+EA-treated group (received FLZ, 3 mg/kg and ellagic acid, 30 mg/kg, i.p.). Moreover, in the first set of experiments, to evaluate the effect of chronic administration of EA on anxiety, experimental groups (2 groups, 8 mice per group) were control (received vehicle once a day for 10 days) and EA-treated group (received ellagic acid at the dose of 30 mg/kg, i.p. once a day for 10 days). In the second set of experiments, to evaluate acute (single dose) and chronic (for 10 days) administration of EA on motor activity, animal groupings were similar to the first set of experiment. Elevated plus maze (EPM) and open field tests used to study anxiolytic and motor activity effect of EA, respectively. Statistical analysis was performed by one-way ANOVA and post hoc Tukey’s test. P values less than 0.05 were considered as significant. Results: Acute and chronic application of EA significantly enhanced the number of open arm entries and percentage of time spent in open arm compared with the control (P < 0.05). Pretreatment with flumazenil (FLZ + EA-treated group) significantly decreased the number of open arm entries and percentage of time spent in open arm compared with EA-treated group (only received EA at the dose of 30 mg/kg). Ellagic acid at the dose of 100 mg/kg significantly decreased ambulatory movement compared with the control, while EA at the dose of 30 mg/kg did not affect ambulation. Conclusions: Acute and chronic administration of ellagic acid had anxiolytic property. Also, the most effective dose of ellagic acid was 30 mg/kg. Pretreatment with flumazenil reversed the beneficial effect of ellagic acid and diazepam on anxiety. It is likely that the anxiolytic effect of ellagic acid is largely mediated by activation of GABAA receptor.

Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice

BackgroundEthanol extract from Gynostemma pentaphyllum (GP) shows anti-stress and anxiolytic functions in mice, and also protects dopamine neurons in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. In addition, gypenosides (the gypenoside-enriched components of GP, GPS) have a protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson’s disease. In this study, the ameliorating effects of GPS on chronic stress-induced anxiety disorders in mice were investigated.MethodsMice were orally treated with GPS (100 and 200 mg/kg) once a day for 10 days, followed by exposure to electric footshock (EF) stress (0.6 mA, 1 s every 5 s, 3 min). After the final administration of either GPS, water extract of GP (GP-WX) or ethanol extract of GP (GP-EX, positive control), the behavioral tests such as elevated plus-maze, marble burying and locomotor activity tests, and the biochemical parameters including dopamine, serotonin and corticosterone levels, and c-Fos expression were examined.ResultsTreatment with GPS (100 and 200 mg/kg) increased the number of open arm entries and the time spent on open arms in elevated plus-maze which were reduced by chronic EF stress. GPS (100 and 200 mg/kg) reduced the number of marbles buried which increased by chronic EF stress. In these states, the brain levels of dopamine and serotonin decreased by chronic EF stress and they were recovered by GPS. The serum levels of corticosterone increased by chronic EF stress were also reduced by GPS (100 and 200 mg/kg). Finally, chronic EF stress-induced c-Fos expression was markedly reduced by GPS (100 and 200 mg/kg) in the brain. GPS (100 and 200 mg/kg) also showed an equivalent efficacy on anxiolytic functions, as compared with GP-EX (50 mg/kg). However, GP-WX (50 mg/kg) showed a less effect on anxiety disorders than GP-EX (50 mg/kg) and GPS (100 and 200 mg/kg).ConclusionThese results suggest that GPS (100 and 200 mg/kg) has anxiolytic effects on chronic EF stress-induced anxiety disorders by modulating dopamine and serotonin neuronal activities, c-Fos expression and corticosterone levels. GPS may serve as a phytonutrient in chronic stress-induced anxiety disorders.

Effect of a Hydroalcoholic Extract of Rosa Canina Flowers on Anxiety in Rats

We investigated effects of the hydroalcoholic extract of Rosa сanina (dog rose) petals on behavior of rats in the elevated plus-maze (EPM) test; adult male Wistar rats weighing 200-240 g were used. Oral everyday administration of the Rosa extract in three doses (150, 300, and 450 mg/kg) was done for one week. Animal behavior in the EPM was videotaped for 10 min, and conventional indices considered to be related to the anxiety level were scored. Introduction of the Rosa canina extract significantly increased the number of open arm entries in a dose-dependent manner and also increased the time of stay in the open arms at a high dose (450 mg/kg). At the same time, the number of closed arm entries interpreted as a correlate of the locomotion intensity did not differ from the control at all doses. Thus, the Rosa canina extract, when orally administered, demonstrates an anxiolytic profile in rats. Future investigations are essential for better understanding of the anxiolytic properties of the extract and neurobiological mechanisms of its action (probable interactions of the Rose extract active agents with neurotransmitter systems.

Effect of Punica granatum on behavior in rats

The importance of diet in depression is now increasingly recognized, since balanced diet not only reduces the risk of various chronic diseases but also promotes normal development and functioning of all systems including brain. Hence the present study was designed to observe the effect of three doses of Punica granatum 2, 5 and 8 ml/kg on the behavioral changes in rats, particularly anxiolytic and antidepressant activity. During 15 days study, experimental paradigm for anxiety and depression were assessed twice using open field, elevated plus maze and forced swimming test. In open field, distance travelled, number of centre entries and number of rearing’s were increased. In elevated plus maze, number of open arm entries were increased and in forced swimming test, there was decrease in duration of immobility and increase in duration of climbing. All these changes were significant at moderate and high doses of P. granatum. Thus it may be suggested that P. granatum possesses anxiolytic and antidepressant activity at moderate and high doses. Key words: Punica granatum, anxiolytic, antidepressant.

Modulatory effect of VIP injected into hippocampal CA1 area on anxiety in olfactory bulbectomized rats.

Vasoactive intestinal peptide (VIP) is a neuropeptide, which is widely distributed in the central nervous system and peripheral tissues, acting both as a neurotransmitter and neuromodulator. Despite its extensive expression in the hippocampus, amygdala and other limbic system structures, the effects of VIP on anxiety and depression have not yet been fully investigated. The aim of the present study was to evaluate the involvement of VIP and VIP receptors in the mechanism of anxiety in rats with a model of depression (bilateral olfactory bulbectomy), using the elevated plus-maze test. VIP and a non-specific antagonist of VIP receptors (VIP6-28) were administered unilaterally into the hippocampal CA1 area of bulbectomized (OBX) rats. VIP (10 ng) showed a tendency for an anxiety-modulatory effect upon right side injection, by reducing significantly the closed arm time and increasing the open arm time. VIP (100 ng) injected unilaterally (left or right) into CA1 area induced an anxiolytic-like effect on the activity of OBX rats (increased the number of open arms entries, open arm time and the ratio open/total number of entries). VIP6-28 failed to antagonize the anxiety-related behavior of OBX rats in the plus maze. An unexpected finding in our study was that upon pretreatment with VIP6-28, VIP (10 ng), injected unilaterally (left or right) exerted an anti-anxiety like effect (increased the number of open arm entries, open arm time and the ratio open/total number of entries). Our data point to a possible involvement of hippocampal VIP-ergic neurons in modulating emotional processes or adaptive responses to stressful stimuli in a rat model of depression.

Behavioral effects of Citrus limon in rats.

Anxiety and depression are increasing worldwide, however these disorders may be managed by making healthier changes is dietary pattern, since there are evidences that diet rich in antioxidants and vitamins help reduce anxiety and depression. Hence present study was designed to evaluate the behavioral effects of Citrus limon in rats at three different doses i.e. 0.2, 0.4 and 0.6 ml/kg considered as low, moderate and high doses. Anxiolytic and antidepressant activities were specifically assessed twice during 15 days using open field test, elevated plus maze and forced swimming test. In open field test C. limon, revealed increase in distance travelled, number of central entries and number of rearing's at moderate dose, while in the elevated plus maze, number of open arm entries were found to be increased. Whereas in forced swimming test, there was decrease in duration of immobility and increase in duration of climbing. Thus results of present study suggest that C. limon at moderate dose have anxiolytic effect.

Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and depression-like behaviors in adult mice

Humans are routinely exposed to low levels of bisphenol A (BPA), an environmental endocrine disruptor, which is widely used in the production of polycarbonate plastics. The effects of perinatal exposure to BPA have been shown to affect various aspects of social behaviors such as anxiety and depression in adult offspring. Because sex hormones play a critical role in neurobehavior in adulthood, it is possible that long-term exposure to BPA has widespread effects on these emotional behaviors in adulthood. In the present study, adult mice were exposed to BPA at dosages of 0.04, 0.4, 4, 40mgkg−1d−1 for 12weeks. A behavioral assay was performed using the open field test (OFT), mirrored maze, the elevated plus maze (EPM), and the forced swim task. The results showed that, after exposure to BPA at 0.4–40mgkg−1d−1, the number of open arm entries and the time spent in them in the elevated plus maze task were reduced in males but increased in females, and thus eliminating or reversing sex differences in these behaviors. BPA at 0.04–40mgkg−1d−1 increased the immobility of male mice in the forced swimming test. Furthermore, BPA (0.4–40mgkg−1d−1) significantly decreased brain level of testosterone in males, but no significant influence was found in serum and the brain levels of estradiol in females. Western blot analysis further indicated that BPA at 0.4, 4, or 40mgkg−1d−1 significantly down-regulated the protein level of estrogen receptor β (ERβ) in the hippocampus of the adult males but not females, and inhibited the protein level of GABA(A)α2 receptor in hippocampus of males but promoted that of females. These results suggest that long-term exposure to BPA sex specifically affects anxiety- and depression-like behaviors in adult mice. Changes in the levels of GABA(A)α2 receptor and ERβ proteins of hippocampus might be associated with BPA-induced changes in these emotional behaviors.

Effect of biphenyl dimethyl dicarboxylate and fluoxetine on performance of normally-fed and protein malnourished psychologically stressed mice in elevated plus maze

Stress alters psychological diseases such as anxiety and depression. Protein malnutrition (PM) contributes to psychological disorders. The present study aimed to investigate the effect of biphenyl dimethyl dicarboxylate (DDB) on anxiety of psychologically stressed protein malnourished mice as compared to its effect in normally-fed mice. Fluoxetine (FLX) was used as reference standard. Animals were randomly divided into two major groups, normally-fed group provided with 20% casein diet and a protein malnourished one was provided with a diet containing 8% casein for 21 consecutive days. The given diet was continued during the experiment. Stress was induced using the learned helplessness technique (LH). Each animal was exposed for 5days to the psychological stress session either alone or in association with drug administration following completion of 21days under the selected diet regimen. DDB and fluoxetine were given in doses of 100mg/kg p.o. and 10mg/kg i.p., respectively before exposure to foot shocks daily. Anxiety was evaluated using elevated plus maze (EPM) and the whole brain wet tissue monoamine levels, namely dopamine, norepinephrine and serotonin were estimated.Protein malnutrition in the presence of stress resulted in increasing number of open arm entries and head dipping as compared to the normally-fed stressed mice. Stress in the presence or absence of protein malnutrition significantly increased rearing frequency as compared to the corresponding mice. Fluoxetine in the presence of stress significantly decreased open arm time spent and number of open arm entries as compared to protein malnourished stressed mice. Protein malnutrition increased stretched attend posture.

Effects of Buspirone on Anxiolytic Effects of Magnesium in Male Mice

Anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in several studies. Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class that is not related to benzodiazepines, unlike most drugs predominately used. The purpose of the present study was to examine interaction between magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze. The anxiolytic-like effect of Mg (50, 100 and 200 mg/kg, orally), buspirone (5 mg/kg, i.p) and its interaction with Mg (50 mg/kg) was evaluated after ten days treatment. Mg given at all doses (50, 100 and 200 mg/kg) and buspirone (5 mg/kg) induced an anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms (%OAT), the percentage of the open arm entries (%OAE) and number of total entries. Percent time spend in open arms was reduced when buspirone coadministered with Mg (50 mg/kg) compared to Mg alone. However, the number of entries did not change significantly. No synergistic interaction (increased time in open arms and number of open arm entries) between Mg and buspirone was observed, in this test, on the contrary, %OAT preserved about buspirone effects and %OAE remained around Mg effect. The obtained data indicate that Mg may act partly via serotonergic receptors due to buspirone’s inhibitory action as a partial agonist of serotonin receptor.

Dexamethasone Regimens Alter Spatial Memory and Anxiety Levels in Mice

Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were given vehicle (normal saline), a standard drug (Diazepam or Scopolamine) or one of three selected doses of dexamethasone (0.5, 1.0 and 1.5 mg/kg) daily for a period of 14 days. Behavioral tests were carried out on days 1 and 14 after administration. Results were analysed using a one-way ANOVA followed by a posthoc test (Student-Newman-Keul) and expressed as mean ± S.E.M. Elevated plus maze test showed a significant reduction in the time spent in the open arm and in the number of open arm entries compared to control. Results of radial arm and Y maze tasks showed an improvement in spatial memory following dexamethasone administration. Y maze locomotor activity was significantly increased, although radial arm maze exploration did not increase significantly. The study concluded that oral dexamethasone given either acutely or sub chronically has both anxiogenic and memory enhancing effects.

Interactions of atenolol with alprazolam/escitalopram on anxiety, depression and oxidative stress

Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological mechanism. The dysfunction of serotoninergic, noradrenergic and dopaminergic neurotransmission, abnormal regulation in the hypothalamic–pituitary–adrenal axis (HPA), disturbance of cellular plasticity including reduced neurogenesis, or chronic inflammation connected with high oxidative damage play a crucial role in the development of anxiety and depression. The present study was aimed to investigate the effects of atenolol alone and in combination with alprazolam/escitalopram on anxiety, depression and oxidative stress. Wistar albino rats were subjected to 21day treatment of drugs then exposed to elevated-plus maze (EPM) and modified forced swim test (MFST), and oxidative stress markers were estimated in isolated brain tissue of all groups. The results indicated that atenolol in combination with alprazolam/escitalopram exhibited antidepressant effects by significantly decreasing the immobility and increasing the swimming behavior in the MFST and anti-anxiety effects by increasing the percentage preference and number of open arm entries as well as time spent in open arm in EPM. Pretreatment with atenolol alone and combination with alprazolam/escitalopram also ameliorated tissue glutathione (GSH) and decreased malondialdehyde (MDA) level significantly which explore antioxidant properties of drugs, and combination augments the therapeutic response of monotherapy in depression. In conclusion behavioral and biological findings indicate that the combination of atenolol with alprazolam/escitalopram has the potential of being highly efficacious in treating anxiety and depressive disorders as well as oxidative stress.

Androgen insensitive male rats display increased anxiety-like behavior on the elevated plus maze

Male rats carrying the testicular feminization mutation (Tfm-affected males) are insensitive to androgens, resulting in a female-typical peripheral phenotype despite possession of inguinal testes that are androgen secretory. Androgen-dependent neural and behavioral processes may likewise show atypical sexual differentiation. Interestingly, these mutant rats display elevated serum corticosterone, suggesting a chronic anxiety phenotype and dysregulated hypothalamic–pituitary–adrenal axis. In order to understand if elevated anxiety-like behavior is a possible mediating variable affecting the display of certain androgen-dependent behaviors, we compared the performance of Tfm-affected males to wild type males and females in the elevated plus maze (EPM). Two well-established indicators of anxiety-like behavior in the EPM were analyzed: total percentage of time spent on the open arms, and the percentage of open arm entries. We also analyzed the total number of open arm entries. Interestingly, Tfm-affected males spent less percentage of time on the open arms than both males and females, suggesting increased anxiety-like behavior. Percentage of open arm entries and the total number of arm entries was comparable between the groups, indicating that the observed decrease in the percentage of time spent on the open arms was not due to a global reduction in exploratory behavior. These data, in contrast to earlier reports, thus implicate androgen receptor-mediated functions in the expression of anxiety behaviors in male rats. Given that anxiety is widely reported as a precipitating factor in depression, studying the role of the androgen receptor in anxiety may give insights into the pathogenesis of major depressive disorder.

Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice

Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY–5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects.

Anxiolytic Action of Pterostilbene: Involvement of Hippocampal ERK Phosphorylation

Pterostilbene, a natural analog of resveratrol, has diverse health-beneficial properties. However, the neurological activities of this compound are largely unexplored. Here, we report that pterostilbene shows anxiolytic-like actions by down-regulating phosphorylated levels of extracellular regulated kinases in the hippocampus of mice. Adult male mice administered pterostilbene (1-10 mg/kg, p. o.) were subjected to the elevated plus maze test. Pterostilbene manifested anxiolytic activity at 1 and 2 mg/kg doses, demonstrated by increases in % permanence time and number of open arm entries. The locomotor activity of the animals was unaffected at all doses. Western blot analysis revealed a decrease in both extracellular regulated kinase 1 and extracellular regulated kinase 2 phosphorylation in hippocampal homogenates from mice treated with 1 and 2 mg/kg pterostilbene. Moreover, pterostilbene was detected in the plasma and brains of mice following single oral administration. Anxiolytic activity was not observed at the higher doses (5 and 10 mg/kg). However, no impairment of motor function was observed either, suggesting a favorable safety index for the compound. These results suggest that pterostilbene has the potential for therapeutic drug development for anxiety disorders.

The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats

Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy.