Number Of Open Arm Entries Research Articles

Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice

The purpose of this study was to characterize the putative anxiolytic-like activity of fractions prepared from a hydroethanol extract of Passiflora incarnata L. using the elevated plus-maze (EPM) in mice. The fractions were prepared as published recently, yielding a butanol, petroleum ether and chloroform fraction. From the tested fractions, the butanol fraction showed significant increases in the number of open arm entries in the EPM in concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of the original extract. The highest activity was found for the chloroform fraction in doses of 0.17 mg/kg (10.0 ± 1.9, p < 0.001) and 0.34 mg/kg (6.6 ± 0.86; p < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg, respectively. Interestingly, the petroleum ether fraction did not show any effects in the elevated plus maze. A sedative or stimulatory effect of each of the fractions could be excluded, since none of the compounds had an influence on the total distance that the animals covered during the observation period. The results suggest that the active principle of passion flower seems to be in the chloroform fraction and to a lower extent in the butanol fraction.

Anti‐anxiety and sedative profile evaluation of imidazo[1,2‐a]pyridine derivatives

AbstractThree imidazo[1,2‐a]pyridine‐3‐nitrosated (L‐1, L‐2, L‐3) and a 3‐formyl imidazo[1,2‐a]pyridine thiosemicarbazone (L‐4) were synthesized and evaluated for their effects in the elevated plus maze, burying behavior test, rotarod performance, the horizontal wire test, and locomotor activity. L‐2 and L‐3 increased the percent time spent in the open arms of the plus maze at doses of 1 and 2 mg/kg without modifying the number of total entries. In addition, L‐2 and L‐3 (1 mg/kg) increased the number of open arm entries indicating anxiolytic‐like activity at this dose. In the burying behavioral test, L‐1 (2–8 mg/kg), L‐2 (8 mg/kg), and L‐3 (4 and 8 mg/kg), induced a clear reduction in cumulative burying behavior, without modifying burying behavior latency, thus reducing experimental anxiety. In the rotarod test, L‐1 and L‐2 impaired rotarod performance only at the highest evaluated dose (64 mg/kg) at which reduction of motor activity was observed and thereby no conclusions about myorelaxant effects can be proposed. All compounds showed a clear sedative effect and corresponding ED50 values were obtained. Results indicate that compounds L‐1, L‐2, and L‐3 show a sedative and an anxiolytic profile. Drug Dev Res 71:371–381, 2010. © 2010 Wiley‐Liss, Inc.

Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice

The purpose of this study was to characterize the putative anxiolytic-like activity of fractions prepared from a hydroethanol extract of Passiflora incarnata L. using the elevated plus-maze (EPM) in mice. The fractions were prepared as published recently, yielding a butanol, petroleum ether and chloroform fraction. From the tested fractions, the butanol fraction showed significant increases in the number of open arm entries in the EPM in concentrations of 2.1 mg/kg and 4.2 mg/kg corresponding to 150 and 300 mg/kg of the original extract. The highest activity was found for the chloroform fraction in doses of 0.17 mg/kg (10.0 ± 1.9, p < 0.001) and 0.34 mg/kg (6.6 ± 0.86; p < 0.05) which corresponds to a total extract dose of 150 and 300 mg/kg, respectively. Interestingly, the petroleum ether fraction did not show any effects in the elevated plus maze. A sedative or stimulatory effect of each of the fractions could be excluded, since none of the compounds had an influence on the total distance that the animals covered during the observation period. The results suggest that the active principle of passion flower seems to be in the chloroform fraction and to a lower extent in the butanol fraction. Copyright © 2010 John Wiley & Sons, Ltd.

Anxiolytic Activity of Canscora decussata in Albino Rats

Shankhpushpi is a popular medicinal plant in the Ayurvedic system of medicine for treating mental disorders. The present study was undertaken to investigate the effects of Canscora decussata Schult. (Gentianaceae) commonly known as shankhpushpi on the central nervous system of albino rats. Ethanolic extract of the aerial parts of the plant was evaluated in the elevated plus-maze test, open field exploratory behavior and rotarod performance experiments. In the elevated plus-maze, ethanolic extract at a dose of 100, 200 and 400 mg/kg p.o. showed an anxiolytic effect as evidenced by increase in the time spent in open arms and the number of open arm entries, compared to control group. The open field exploratory behaviour was also increased on administration of the ethanolic extract. The ethanolic extract at dose of 400 mg/kg p.o. significantly reduced the neuromuscular coordination indicative of the muscle relaxant activity at a high dose. Diazepam (1 mg/kg i.p.) was used as a standard in all the animal models studied. A biomarker viz., mangiferin, was also isolated and characterized and its effects were observed in the animal models along with the ethanolic extract.

Assessing anxiolytic-like effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors using the elevated plus maze in mice

The anxiolytic-like effects of selective serotonin reuptake inhibitors (SSRIs; paroxetine, fluvoxamine) and serotonin-noradrenaline reuptake inhibitors (SNRIs; milnacipran, venlafaxine) were compared with those of benzodiazepines (diazepam, chlordiazepoxide) and tricyclic antidepressants (imipramine, amitriptyline) using the elevated plus maze in mice. Paroxetine and fluvoxamine had no significant effects on the time spent in open arms and the number of open arm entries, even at a dose of 20 mg/kg p.o. On the other hand, milnacipran and venlafaxine showed a dose-dependent increase in the time spent in open arms and the number of open-arm entries. Significant effects were observed at doses of 10 and 20 mg/kg p.o. for both drugs. Diazepam and chlordiazepoxide showed potent anxiolytic-like effects, whereas imipramine and amitriptyline caused no anxiolytic-like effects. Like diazepam and chlordiazepoxide, milnacipran and venlafaxine increased the distance moved in open arms at the same dose levels showing anxiolytic-like effects. From these results, it may be concluded that SNRIs caused anxiolyic-like effects similar to benzodiazepines.

Anxiolytic activity of Evolvulus alsinoides and Convulvulus pluricaulis in rodents

Shankhpushpi is a popular medicinal plant in the Ayurvedic system of medicine for treating mental disorders. Convulvulus pluricaulis Choisy. (Convulvulaceae) and Evolvulus alsinoides Linn. (Convulvulaceae) are used as Shankhpushpi by Ayurvedic practitioners. Ethanol extract of the aerial parts of both these drugs was evaluated for central nervous system (CNS) activity. The ethanol extract was fractionated into ethyl acetate and aqueous fractions and was tested in experimental models employing rats and mice. Elevated plus maze test, open field exploratory behavior and rotarod performance experiments were undertaken to observe influence on CNS. The extracts were also studied for their in vitro antioxidant potential to correlate their anxiolytic activity. In the elevated plus maze, ethyl acetate fractions of both the drugs at 100 mg/kg per oral showed an anxiolytic effect as evidenced by increase in the time spent in open arms and the number of open arm entries, compared to the control group. The open field exploratory behavior was also increased on administration of the ethyl acetate fractions (100 mg/kg p.o.) of both the drugs. The ethyl acetate fractions at doses of 200 mg/kg p.o. significantly reduced the neuromuscular coordination indicative of the muscle relaxant activity at a higher dose in both the drugs. The aqueous fractions of both the drugs were devoid of the above pharmacological actions at similar doses. Diazepam (1 mg/kg i.p.) was used as a standard in all the animal models studied. The present study provides scientific support for the anxiolytic and antioxidant activities of extracts of Evolvulus alsinoides and Convulvulus pluricaulis and substantiates the traditional claims for the usage of these drugs in stress-induced disorders.

Anxiolytic-like Effects of Ginsenosides Rg3 and Rh2 from Red Ginseng in the Elevated Plus-Maze Model

The anxiolytic-like effects of red ginseng (RG, the steamed root of Panax ginseng, family Araliaceae), its saponin fraction, and its representative constituents, ginsenosides Rg3 and Rh2, were investigated in mice using the elevated plus-maze test. These agents significantly increased the time spent on the open arms and the number of open-arm entries. The anxiolytic-like activities of Rg3 and Rh2 were antagonized by flumazenil but not by WAY-100635. RG and its constituents, Rg3 and Rh2, may exert anxiolytic effects by antagonizing GABA/benzodiazepines.

Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: Possible involvement of GABAergic transmission

This experiment was performed to investigate the anxiolytic-like effects of sanjoinine A, one of the major alkaloid compounds in Zizyphi Spinosi Semen (ZSS), by using experimental paradigms of anxiety in comparison with a known anxiolytic, diazepam. Sanjoinine A (2.0 mg/kg) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of time spent in the center zone and the center zone locomotor distance in the open field box experiment. However, sanjoinine A (0.5, 1.0, 2.0 mg/kg) had no effect on locomotor activity, while diazepam (2.0 mg/kg) significantly reduced locomotor activity. Sanjoinine A (0.5, 1.0, 2.0 mg/kg) did not influence the grip force in the grip strength meter test either. Molecular experiments showed that sanjoinine A (2.0, 5.0 μM) increased chloride influx in cultured cerebellar granule cells. In addition, sanjoinine A (5.0 μM) treatment resulted in over-expression of α- and γ-subunits of GABA A receptors and glutamic acid decarboxylase (GAD65/67) in cultured cerebellar granule cells. It is concluded that sanjoinine A may have anxiolytic-like effects in the elevated plus-maze, hole-board test and open field test, and these effects may be mediated by GABAergic transmission.

Anxiolytic-Like Effects of Cyclopeptide Fraction Alkaloids of Zizyphi Spinosi Semen: Possible Involvement of GABAAReceptors

This experiment was performed to investigate the anxiolytic-like effects of cyclopeptide fraction alkaloids of Zizyphi Spinosi Semen (CFAZ), by using the experimental paradigms of anxiety, and compared with those of a known anxiolytic, diazepam. CFAZ (8.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of center zone ambulatory time in the open-field box. However, CFAZ has no effect on the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly reduced locomotor activity. CFAZ did not influence the grip force in the grip strength meter test, either. From the molecular experiments, CFAZ increased chloride influx in cultured cerebellar granule cells. In addition, <TEX>$GABA_A$</TEX> receptors <TEX>$\gamma$</TEX>-subunit were over-expressed by CFAZ in cultured cerebellar granule cells. It is concluded that CFAZ may have anxiolytic-like effects, and these effects may be mediated by <TEX>$GABA_A$</TEX> receptors.

Evaluation of Anxiolytic-like Effects of Some Short-Acting Benzodiazepine Hypnotics in Mice

Anxiolytic-like effects of some short-acting benzodiazepine hypnotics were examined with experimental paradigms of anxiety using an elevated plus-maze in male ICR mice. Diazepam was used as a positive control. The drug at a dose of 1 mg/kg significantly increased the percentage of time spent in the open arms and percentage of the number of open arm entries in the elevated plus-maze. Triazolam, brotizolam, rilmazafone, and lormetazepam also showed an anxiolytic-like effect as indicated by the significant increase in the percentage of time spent in the open arms and percentage of the number of open arm entries. Effects of short-acting benzodiazepine hypnotics used in the study were more potent than those of diazepam. In addition, the doses affecting the elevated plus-maze by benzodiazepine hypnotics were much smaller than those that showed muscle-relaxant activity measured by the rotarod test, indicating that anxiolytic-like effects of benzodiazepine hypnotics had high specificity and selectivity.

Two kinds of behavioral evaluation of intoxication by oral administration of ethanol in mice

Evaluation of ethanol intoxication in humans has difficulties in individual differences and ethical considerations. Intraperitoneal injection of ethanol has been used in evaluation of ethanol intoxication in nonhuman animals. We have developed two kinds of behavioral evaluations of intoxication by oral administration of ethanol in mice. Oral administration of ethanol (1.6∼4.0g/kg as a single dose, 0.8∼1.6g/kg dosed twice) increased both the number of open-arm entries and the time spent in the open arm of the elevated plus-maze test, demonstrating an anxiolytic-like effect of ethanol. Oral administration of ethanol (1.6 or 4.0g/kg single dose, 1.2 or 2.4g/kg dosed twice) significantly decreased locomotor activity under fasting conditions. Under semi-fasting conditions, oral administration of ethanol (1.6g/kg single dose) transiently enhanced locomotor activity 1 h after administration but decreased subsequently for 48 h. Elevated plus maze and locomotor activity are useful for analyzing mild and mild-to-severe intoxicaton, respectively, caused by oral administration of ethanol on the condition used in this study.

Anxiolytic-like Effects of Methanol Extract of Zizyphi Spinosi Semen in Mice

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. <TEX>$GABA_{A}$</TEX> receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

Anxiolytic-like effects of obovatol isolated from Magnolia obovata: Involvement of GABA/benzodiazepine receptors complex

This experiment was performed to investigate whether obovatol isolated from the leaves of Magnolia obovata has anxiolytic-like effects through GABA-benzodiazepine-receptors Cl − channel activation. The anxiolytic-like effects of obovatol in mice were examined using the elevated plus-maze and the automatic hole-board apparatus. Oral administration of obovatol (0.2, 0.5 and 1.0 mg/kg) significantly increased the number of open arm entries and the spent time on open arm in the elevated plus-maze test, compared with those of saline. Obovatol (0.2, 0.5 and 1.0 mg/kg) also produced anxiolytic-like effects, as reflected by an increase in head-dipping behaviors. These effects were comparable to those of diazepam (1.0 mg/kg), a well known anxiolytic drug. On the other hand, the anxiolytic-like effects of obovatol and diazepam were reversed by flumazenil, a benzodiazepine receptor antagonist, suggesting that the anxiolytic-like effects of obovatol were involved in GABA-benzodiazepine receptors complex. Obovatol was muscle relaxant by rota-rod test, but its effect was weaker than diazepam. Spontaneous locomotor activity also was inhibited by obovatol. Obovatol selectively increased the GABA A receptors α 1 subunit expression in amygdala of mouse brain. Obovatol also showed to bind to benzodiazepine receptors competitively in experiments using [ 3H]flunitrazepam in the cerebral cortex of mouse brain. Moreover, obovatol (10, 20 and 50 μM) increased Cl − influx and the increased Cl − influx was inhibited by flumazenil, in primary cultured neuronal cells and IMR-32 human neuroblastoma cells. These results suggest that obovatol has anxiolytic-like effects, and these pharmacological effects may be mediated by GABA-benzodiazepine receptors-activated Cl − channel opening.

Evaluation of the Anxiolytic and Antidepressant Effects of Alcoholic Extract of Kaempferia parviflora in Aged Rats

To date, the search for novel pharmacotherapy from medicinal plants for psychiatric illnesses has significantly progressed. The present study was performed to evaluate the anxiolytic and antidepressant like activities of the K.parviflora rhizome extract. Aged male Wistar rats were orally administered the alcoholic extract of this plant at various doses ranging from 100, 200 and 300 mg kg-1 BW once daily for 7 days. The anxiolytic and antidepressant activities were performed after both single and repetitive treatment for 7 days using elevated plus maze and forced swimming tests respectively. The results showed that the extract decreased immobility time with the increase swimming time. However, no changes in number of open arm entries and time spent in open arm were observed. These results suggested the anti-depression activity of the plant extract. Therefore, K.parviflora may be served as a potential resource for natural psychotherapeutic agent against depression. However, further studies were still required.

Temporary inactivation of the rostral perirhinal cortex induces an anxiolytic-like effect on the elevated plus-maze and on the yohimbine-enhanced startle response

The present study investigated whether the rostral perirhinal cortex is involved in aversive information processing, particularly in unconditioned fear (anxiety). We temporarily inactivated the rostral perirhinal cortex by local injections of the GABA A agonist muscimol (0.0, 1.1, and 4.4 nmol/0.5 μl) and tested whether these injections affected the behavior of rats in the elevated plus-maze and in the yohimbine-enhanced startle test. Temporary inactivation of the rostral perirhinal cortex increased the number of open arm entries and the open arm ratio in the elevated plus-maze. In addition, startle response enhancement caused by the anxiogenic drug yohimbine was reduced by perirhinal cortex inactivation. Taken together, these data clearly show that the rostral perirhinal cortex is involved in the processing of emotional stimuli and is critical for the expression of unconditioned fear (anxiety).

Anxiolytic-like effects of ginseng in the elevated plus-maze model: Comparison of red ginseng and sun ginseng

This study was performed to investigate the anxiolytic-like effects of red ginseng (RG, steamed raw ginseng at 98–100 °C) and sun ginseng (SG, heat-processed ginseng at higher temperature) in mice using the elevated plus-maze model. Furthermore, the anxiolytic-like effects of RG and SG were compared to a known active anxiolytic drug (diazepam). The RG butanol fraction (100 mg/kg) significantly increased the number of open arms entries and the time spent on the open arm (indicators of anxiolytic-like effects) compared with that of the saline group. However, lower doses of the SG total extract (50 mg/kg) and the SG butanol fraction (25 and 50 mg/kg) significantly increased the number of open arms entries and the time spent on the open arms. The RG total extract (100 mg/kg) and the SG total extract at a lower dose (25 mg/kg) did not increase the number of open arm entries or the time spent on the open arm. On the other hand, the RG butanol fraction (100 mg/kg), the SG total extract (50 mg/kg), and the SG butanol fraction (50 mg/kg) decreased locomotor activity in a manner similar to diazepam. These data indicate that ginseng has anxiolytic-like effects, and the anxiolytic potential of SG is stronger than that of RG in the elevated plus-maze model. Ginseng saponins have been suggested to play an important role in the anxiolytic effects of ginseng. We provide evidence that ginseng may be useful for the treatment of anxiety.

Antidepressant action of agomelatine (S 20098) in a transgenic mouse model

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic–pituitary–adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.

Effect of chronic Albizzia julibrissin treatment on 5-hydroxytryptamine 1A receptors in rat brain

Quantitative receptor autoradiography and behavioral studies were employed to investigate whether the aqueous extract of Albizzia julibrissin (AEAJ) specifically targets serotonergic systems in rat brain. AEAJ was orally administered at 50 and 200 mg/kg to adult male SD rats for 7 days. Treatment with AEAJ (200 mg/kg) significantly increased time-spent in open arms and the number of open arm entries in an elevated plus-maze (EPM) versus saline controls ( P < 0.05). Moreover, those effects of AEAJ were blocked by WAY 100635, a 5-HT 1A receptor antagonist. Following behavioral evaluation, the binding of [ 3H]8-hyroxy-2-(di- n-propylamino) tertalin ([ 3H]8-OH-DPAT) to 5-HT 1A receptors in rat brain was investigated. [ 3H]8-OH-DPAT binding after AEAJ (200 mg/kg) treatment showed a marked increase in the frontal cortex, hippocampus (CA2 and CA3 regions) and in the lateral septum versus vehicle-treated controls. No changes of [ 3H]8-OH-DPAT binding were observed in the caudate putamen, dentate gyrus and CA1 areas of the hippocampus or in the hypothalamus. In the dorsal raphe region, [ 3H]8-OH-DPAT binding was significantly reduced by AEAJ (50 mg/kg) treatment but was unchanged by AEAJ (200 mg/kg). These results suggest that the anxiolytic-like effect of A. julibrissin is mediated by the changes of serotonergic nervous system, especially 5-HT 1A receptors.

Anxiolytic-Like Effects of Ginsenosides on the Elevated Plus-Maze Model in Mice

In a previous study, we reported that ginseng extract has anxiolytic-like effects in the elevated plus-maze model and that the ginseng saponin fraction plays an important role. This experiment was performed to investigate the anxiolytic-like effects of ginsenosides Rb1, Rg1, Rg3-R, and Rg3-S, and the Rg5 and Rk mixture isolated from the ginseng saponin fraction in the elevated plus-maze. Furthermore, the anxiolytic-effects of Rb1, Rg1, Rg3-R, Rg3-S, and the Rg5 and Rk mixture were compared with those of a well-known active anxiolytic drug (diazepam). The oral administration of ginsenoside Rb1 significantly increased the number of open arm entries and the time spent on the open arm compared with those in the vehicle-treated group. Ginsenoside Rg1 and the Rg5 and Rk mixture also significantly increased the number of open arm entries and the time spent on the open arm. However, ginsenosides Rg3-R and Rg3-S did not increase the number of open arm entries or the time spent on the open arm. On the other hand, ginsenoside Rb1 and the Rg5 and Rk mixture decreased locomotor activity in a manner similar to diazepam. These data indicate that ginsenosides Rb1, Rg1, and the Rg5 and Rk mixture have anxiolytic-like effects, but ginsenosides Rg3-R and Rg3-S do not in this model. We provide evidence that some ginsenosides may be useful for the treatment of anxiety.

Novel Actions of Estrogen Receptor-β on Anxiety-Related Behaviors

Estrogens are reported to have both anxiogenic and anxiolytic properties. This dichotomous neurobiological response to estrogens may be mediated by the existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. In brain, ERalpha plays a critical role in regulating reproductive neuroendocrine function, whereas ERbeta may be more important in regulating nonreproductive functions. To determine whether estrogen's anxiolytic actions could be mediated by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists. Ovariectomized female rats, divided into four treatment groups, were injected with the selective ERbeta agonist diarylpropionitrile (DPN), the ERalpha-selective agonist propyl-pyrazole-triol (PPT), 17beta-estradiol, or vehicle daily for 4d. After injections, behavior was monitored in the elevated plus maze or open field. Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the elevated plus maze, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the open field, DPN-treated females made more rears, interacted more with a novel object, and spent more time in the middle of the open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions are ER mediated, the nonselective ER antagonist tamoxifen was administered alone or in combination with DPN. Tamoxifen blocked the previously identified anxiolytic actions of DPN. Taken together, these findings suggest that the anxiolytic properties of estrogens are ERbeta mediated.