Hole Board Models Research Articles

Evaluation of neurobehavioral activities of ethanolic extract of Psidium guajava Linn leaves in mice model

BackgroundThe complementary and alternative medicines have particular importance in treating various comorbid conditions including anxiety and depression which prevalence will be raised to the second highest risk of morbidity, triggering a noteworthy socioeconomic burden. Ethanolic extract of leaves of Psidium guajava Linn (EEPG) was investigated to evaluate the anxiolytic and anti-depressant activity into two different doses (200 mg/kg and 400 mg/kg of body weight) on Swiss Albino male mice utilizing experimental paradigms of anxiety and depression. The extract was also subjected to phytochemical screening.ResultsPhytochemicals screening showed the presence of numerous types of active constituents in extract, for example, flavonoids, alkaloids, terpenoids, and steroids. The experimental results revealed that in case of anxiolytic activity tests, a statistical significant (p < 0.05 vs group I) effect is observed in EPMT model, hole cross model, light and dark model in both doses, whereas in hole-board model, marble burying model tests, a statistical considerable effect is observed only at the dose of 400 mg/kg although at the dose of 200 mg/kg, anxiolytic effect is also expressed and in case of anti-depressant activity test, the statistical significant effect is observed only at the dose of 400 mg/kg. All the results are comparable with the effect of standard drugs used.ConclusionsTaken together, the present research work evidences the anxiolytic and anti-depressant effects of EEPG, but further investigation needed to find out the underlying mechanism of action and to isolate and purify the specific components that are responsible for aforementioned activities.

Exploration of in vitro thrombolytic, anthelminthic, cytotoxic and in vivo anxiolytic potentials with phytochemical screening of flowers of Brassica nigra

BackgroundBrassica nigra is a plant of Brassicaceae family, which possesses numerous medicinal values. Our present study is intended to assess the potential in vitro thrombolytic, anthelminthic, cytotoxic and in vivo anxiolytic properties of MCE of B. nigra flowers. MCE was fractioned for separating the compound on the basis of polarity by using chloroform, n-hexane and ethyl acetate solvent. Thrombolytic and anthelminthic activities were explained by collecting human erythrocytes and earthworms as test models, respectively. Anxiolytic activity was evaluated by elevated plus maze and hole board models while cytotoxic test was conducted through brine shrimp lethality bioassay.ResultsMCE revealed the presence of alkaloids, flavonoids, tannin, diterpenes, glycosides, carbohydrates, phenols, fixed oils and fat. In case of thrombolytic test, the MCE, CSF, ASF and n-HSF had produced maximum clot lysis activity at 5 and 10 mg/ml dose conditions. Two different concentrations (10 and 20 mg/ml) of MCE and its fractions showed significant (p < 0.05) anthelminthic activities in a dose-dependent manner. Significant anxiolytic activity was observed for all fractions which was comparable to the standard drug diazepam (p < 0.05). Again, the cytotoxic screening also presented good potentials for all fractions.ConclusionFrom the findings of present study, we can conclude that MCE of B. nigra flowers and its fraction possess significant anxiolytic, anthelmintic, anticancer and thrombolytic properties which may be a good candidate for treating these diseases through the determination of bio-active lead compounds.

Sedative, hypothermic, anxiolytic effects and rapid radical scavenging property of aqueous leaf extract of Vitex doniana (Lamiaceae) in mice

Vitex doniana is used ethnomedicinally for the management of madness, insanity, and epilepsy. This study was undertaken to evaluate the sedative, hypothermic and anxiolytic effects of crude aqueous leaf extract of Vitex doniana (AVD) in mice, as well as its rapid radical scavenging property. Doses of 250, 500, and 1000 mg/kg AVD were adopted for the pharmacological testing in mice of both sexes (n=6). The behavioural effects of the extract in the open field apparatus were determined. AVD was evaluated for its anxiolytic effect, using elevated T- maze, staircase, and hole-board models. While the sedative and hypothermic effects of the extract in mice were determined by assessments of ketamine-induced sleeping time and rectal temperature respectively. AVD was subjected to rapid radical scavenging test using thin-layer chromatography (TLC)-bioautography. The results showed AVD to have an inhibitory effect on CNS in the open field test. AVD demonstrated anxiolytic effect at 250 mg/kg, and sedative effect at 500 and 1000 mg/kg. The sedative effect of AVD at 500 and 1000 mg/kg was further revealed in ketamine-induced sleeping time and rectal temperature. AVD also showed strong free radical scavenging property attributed to the presence of fatty acid esters, terpenes, phenolics, and phenolic glycosides. AVD is acutely non-toxic and it possesses significant sedative, hypothermic and anxiolytic effects, which could in part be due to the presence of rapid free radical scavenging compounds, thus, providing pharmacological justification for its ethnomedicinal uses as a curative for madness and insanity.

Bioactivity-guided isolation of potent anxiolytic compounds from leaves of Citrus paradisi.

Context:Citrus fragrances have been attributed with mood-enhancing properties by aromatherapists. Leaves of this plant have been reported to exert anti-anxiety activity. Till date, no specific phytoconstituent responsible for this has been identified.Objective:Isolation of anxiolytic constituent of Citrus paradisi using bioactivity-guided fractionation.Materials and Methods:Leaf extracts of four varieties of C. paradisi in petroleum ether, chloroform, methanol and water were evaluated for anti-anxiety activity in mice using elevated plus-maze apparatus. Because of activity in methanol extract, it was used for safety evaluation/acute toxicity studies in animals. Bioactive fraction of methanol extract was subjected to column chromatography and structure of the isolated compound was elucidated by melting point, ultraviolet, infrared, nuclear mass reactor and mass spectroscopy. The isolated constituents were further evaluated for anti-anxiety activity using light/dark model and hole-board model of anxiety.Results:Results showed no mortality at a dose up to 2000 mg/kg body weight that indirectly reflects the safety profile of the leaf extracts. Fractionation of methanol extract led to the isolation of four flavonoids (rutin, quercetin, kaempferol and myricetin). The isolated compounds exhibited significant anxiolytic activity in different animal models.Conclusion:The study confirms the presence of four flavonoids responsible for anti-anxiety activity.

Assessment of the antioxidant, thrombolytic, analgesic, anti-inflammatory, antidepressant and anxiolytic activities of leaf extracts and fractions of Tetracera sarmentosa (L.) Vahl.

The plant under investigation (Tetracera sarmentosa) is a dicotyledonous flowering plant and belongs to the family Dilleniaceae. The goal of our investigation was to determine whether the leaf extracts of this plant held any significant medicinal properties. Leaves of T. sarmentosa were extracted with pure ethanol (EETS) and methanol (METS), and then methanol extract fractioned with n-hexane (NHFMETS) and chloroform (CHFMETS). The extracts and fractions were tested for antioxidant activity, which was measured by using qualitative and quantitative procedures. Thrombolytic activity was evaluated by the clot lysis test. Analgesic activity was evaluated employing the acidic acid-induced writhing test, the formalin-induced paw licking test and tail immersion on Swiss albino mice. The anti-inflammatory activity test was studied using the paw edema test. Forced swimming, tail suspension, elevated plus maze and hole board model tests were used to evaluate neuropharmacological activity. All the extracts and fractions possessed antioxidant effects. All the extracts, fractions and streptokinase exhibited significant (p<0.0001) clot lysis. The extracts and fractions produced significant analgesic effects as evaluated by the acetic acid writhing test, the formalin-induced paw licking test and the tail immersion method. Similarly, carrageenan-induced inflammation was significantly antagonized by the treatments. The extracts and fractions also significantly showed neuropharmacological (antidepressant and anxiolytic) effects. The overall results suggested that this plant deserves further investigation to isolate the active compounds which are responsible for these activities and to establish the mechanism of action.

Anxiolytic activity of ethanolic and aqueous extract of Ficus carica Linn fruits in swiss albino mice

Background: Benzodiazepams are mainly used to treat anxiety but these drugs produce serious adverse effects, hence herbal drugs are preferred. The present study was undertaken to evaluate the anti-anxiety activity of ethanolic and aqueous extract of Ficus carica (FC) Linn fruits in swiss albino mice.Methods: Male swiss albino rats weighing 25-30gms were divided into six groups and six animals in each group. Diazepam (1.0 mg/kg), AEFC (200 and 400 mg/kg) and EEFC (200 and 400 mg/kg) were suspended in 1% gum acacia and administered orally. The EEFC and AEFC (both extracts at 200 and 400mg/kg/p.o) and vehicle were administered for 7 days once daily p.o. and the last dose was given on the 7lh day, 60 min prior to exposure to the experimental paradigms viz., Elevated plus maze, T- maze model and Hole -board model.Results: Both the extracts of FC significantly increased the number of entries into, time spent and rears in the open arms. Also, it increased the percentile ratio of open arm to total arm entries in elevated plus maze. In T- maze, the both the extracts FC showed a significant increase in baseline latency and decrease in escape and avoidance. In the hole-board model a significant increase in the exploratory behavior like head-dipping and line crossing, rearing was observed after treatment with EEFC and AEFC. FC also decreases the nor-adrenaline levels and increase in serotonin and dopamine levels in the brain. These behavioural changes were significantly higher than that produced by the standard anxiolytic drug diazepam.Conclusions: It was concluded that ethanolic and aqueous extracts of Ficus carica fruits having antianxiety activity.

Coumarins from Angelica archangelica Linn. and their effects on anxiety-like behavior

TRADITIONAL RELEVANCE: Angelica archangelica Linn. (Apiaceae) is an herb distributed in tropical and subtropical regions of the world. Both in Chinese and Indian system of medicine, it is used for nervous disorders including anxiety, anorexia, migraine and other cerebral diseases. To evaluate the anxiolytic potential of non polar coumarins isolated from A. archangelica Linn. A. archangelica Linn. (1 kg) was subjected to extraction in a soxhlet apparatus with petroleum ether (40-60 °C), yield 6.9% w/w. The extract of petroleum ether produced a yellow colored precipitate (YP) which was evaluated for anxiolytic like effect using EPM test and was found significant (**P<0.01) in doses of 5 and 10 mg/kg, po. The precipitate was shown to be a mixture of seven constituents in HPTLC and six on the TLC plate which were further subjected to separation by preparative TLC. Non polar coumarins were isolated namely imperatorin (IM) and isoimperatorin (IIM). YP, IM, IIM were tested for anxiolytic like effects in a dose of 5mg/kg, po along with DZ (1mg/kg, po) using EPM, Light & dark arena and hole board models in rats. All the test drugs were found to have significant (*P<0.05, **P<0.01) activity. IM and IIM have the potential to reduce anxiety but yellow precipitate showed the most promising activity as compared to isolated coumarins. This effect may be due to the synergistic action of all compounds present in the YP or by multiple mechanism of action. The test drugs may have the potential for different receptors. The mixture of coumarins isolated from A. archangelica and its constituents imperatorin and isoimperatorin have the potential to reduce anxiety but it is the mixture which have more significant activity as compared to its individual components.

A Study Of The Anxiolytic-Like Activity Of Dillenia Indica LINN. Leaves In Experimental Models Of Anxiety In Mice

:The purpose of this study was to characterize the putative anxiolytic-like activity of hydroethanolic extract prepared from the leaves of Dillenia indica . Materials and methods :Hydroethanolic extracts of Dillenia indica leaves at 50 ,100 and 200 mg/kg (p.o.) was adminsterd to study anxiolytic effect . Different models of anxiolytic activity viz. hole board , open field , elevated-plus maze and light/dark exploration models were used . Diazepam (2 mg/kg i.p.) was used as the standard drug . Observations : In the hole-board model , there was dose-dependent ( at 100 and 200 mg/kg) and significant (p<.05) increase in the number of headpokes and the time of head dipping in treated groups in comparison to vehicle . In open-field test , the number of rearing and squares traversed increased significantly (p<.05) at doses 100 and 200 mg/kg . In the elevated –plus maze , there was significant increase (p<.05) in time spent and number of entries into the openarms at doses of 100 and 200 mg/kg . In light-dark exploration test the extract at100 mg/kg and those at 200 mg/kg also showed significant activity (p<.05). Conclusion : Hydroethanolic extract of Dillenia indica leaves shows prominent anxiolytic activity in mice .

The neurokinin NK2 antagonist, saredutant, ameliorates stress-induced conditions without impairing cognition

The current work extends our previous findings in stress-related disorders, but also addresses the impact of a neurokinin-2 (NK2) antagonist on cognition. Besides efficacy in mood disorders, an NK2 antagonist may have the potential to lack the disinhibitory components and adverse side effects associated with existing clinical treatments. Saredutant (3–30mg/kg, per os, p.o.) was tested for anxiolytic-like potential in three mouse models: holeboard, stress-induced hyperthermia (SIH) and four-plate. In the holeboard model saredutant (30mg/kg) showed a trend to increase head dipping without affecting general activity. In the SIH model, saredutant demonstrated a significant reduction in stress-induced temperature at 30mg/kg, while the number of punished crossings in the four-plate was increased at all doses tested (3–30mg/kg). While chlordiazepoxide (CDP) demonstrated anxiolytic-like effects in these models, the adverse side effects of benzodiazepines, such as sedation, disinhibition and cognitive deficits are well-documented. Saredutant produced no detrimental effect in three models of cognition: Morris Water Maze (MWM) in rats, spontaneous alternation in a Y-maze in mice and novel objection recognition in mice. In contrast, the benzodiazepine, diazepam (DZM), produced cognitive impairments. NK2 receptor antagonists like saredutant may therefore yield beneficial effects for mood disorders without the adverse effects of current treatments.

F15599, a preferential post-synaptic 5-HT1A receptor agonist: Activity in models of cognition in comparison with reference 5-HT1A receptor agonists

We assessed the activity of F15599, a selective and high efficacy 5-HT(1A) agonist that preferentially activates post- versus pre-synaptic receptors, in rat cognition/memory models. F15599 (0.16 mg/kg i.p.) partially alleviated detrimental effects of phencyclidine on working and reference memory deficit in a hole-board model. It also attenuated phencyclidine-induced deficit of cognitive flexibility in a reversal learning task, without effects of its own. F13714 (0.04 mg/kg) a chemical congener of F15599, and 8-OH-DPAT (0.01 or 0.16), were inactive against these phencyclidine-induced deficits, and/or even worsened basal performances. F15599 (0.04-2.5) was less disruptive than F13714 (0.005-0.16) or 8-OH-DPAT (0.01-0.63), on basal performance in models of attention (5-choice serial reaction time task) and working memory (delayed non-matching to position). Finally, unlike either comparator, F15599 reduced PPI with modest potency and only partially. To conclude, F15599, in models of memory/cognition, has a more favourable profile than F13714 and 8-OH-DPAT. This suggests that preferential activation of post-synaptic 5-HT(1A) receptors could prove useful in pathologies characterized by cognitive/memory deficiencies, such as schizophrenia and depression.

Anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata Fresen.

Aim of the study The objective of this study is to investigate the anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata. Materials and methods The anticonvulsant effect of the aqueous root extract (100, 200 and 400 mg/kg) was evaluated in mice using the strychnine- and picrotoxin-induced seizure models. Its anxiolytic activity was evaluated using the elevated plus maze (EPM) and the Y maze (YM) methods ( Hogg, 1996; Yemitan and Adeyemi, 2003) while the hexobarbitone induced sleep and the hole board models were used to evaluate the sedative and exploratory activities in mice respectively. The acute toxicity studies and phytochemical analysis of the extract were also carried out. Results The extract (100–400 mg/kg) produced a significant ( P < 0.01) dose dependent increase in onset of convulsion compared to the control for strychnine- and picrotoxin-induced seizures. It also produced a significant ( P < 0.01) dose dependent prolongation of the cumulative time spent in the open arms of the elevated plus maze and Y maze compared with the control. The extract (100–400 mg/kg) produced significant ( P < 0.01) reduction in the time of onset of sleep induced by hexobarbitone. The prolongation of hexobarbitone sleeping time by the extract (200 mg/kg) was comparable to that produced by diazepam (3 mg/kg). At doses of 100–400 mg/kg, the extract produced a dose dependent decrease in exploratory activity of the mice. The reduction in exploratory activity produced by the extract (400 mg/kg) was greater than that of chlorpromazine (1 mg/kg). The results obtained from the experiments indicate that the extract has central nervous system depressant and anxiolytic activities. The LD 50 obtained for the acute toxicity studies using both oral and intraperitoneal routes of administration were 1.74 g/kg and 19.95 mg/kg respectively. Conclusion These findings justify the use of Securidaca longepedunculata in traditional medicine for the management of convulsion and psychosis.

Effects of Byrsocarpus coccineus (Connaraceae) extract on the central nervous system (CNS)

In establishing the pharmacological profile of Byrsocarpus coccineus, we investigated the CNS effects of the aqueous leaf extract using the Y-maze, hexobarbitone sleeping time and hole board models in mice. In the Y-maze test, Byrsocarpus coccineus, BC (50–100mg/kg, p.o.) produced significant (P<0.05) increases in the time spent in the open arm at post-treatment times of 30–90min. Peak effect was elicited at 100mg/kg 30min post-treatment, with mice spending 2.63±0.21min in the open arm vs. 0.62±0.21min for control. This effect was significantly higher than that of diazepam, 1mg/kg p.o. (2.00±0.20min). At doses of 200 and 400mg/kg, the effect of BC in increasing the time spent in the open arm diminished with the effect at the higher dose (1.24±0.29min) being not significantly different from the control. In the hexobarbitone sleeping time test, BC (50–100mg/kg) increased the onset and decreased the duration of sleep, with effects only being significant at 100mg/kg (onset=7.00±1.18min and duration=10.00±1.84min vs. onset=3.43±0.81min and duration=20.71±2.34min for control). At doses of 200 and 400mg/kg, BC decreased onset and significantly increased sleeping time with the effect at the higher dose (onset=3.29±0.61min and duration=39.86±3.78min) being significantly lower than that of diazepam, 3mg/kg p.o., in respect of duration of sleep only (onset=3.14±0.26min and duration=87.29±9.87min). In the modified hole board experiment, BC (50–100mg/kg) caused an increase in both exploratory activity and locomotion, while at 200 and 400mg/kg the reverse was the case. These effects were not significant. Diazepam, 1mg/kg p.o., caused a non-significant increase in exploratory activity and a significant increase in locomotion (25.71±4.44 sectional crossings in 5min vs. 10.86±2.30 sectional crossings in 5min for control). Results obtained suggest that the aqueous leaf extract of Byrsocarpus coccineus possess a dose determined anxiolytic – sedative activity with no effect on exploratory activity and locomotion.

Psychopharmacological Profile of the Alkaloid Psychollatine as a 5HT2A/C Serotonin Modulator

Behavioral effects of psychollatine, a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, was investigated in models of anxiety, depression, memory, tremor, and sedation related to 5-HT and/or GABA neurotransmission. The GABA antagonist picrotoxin and the 5-HT2 antagonist ritanserin were used to examine the role of GABA and 5-HT2 receptors in psychollatine-induced effects. In the light/dark and hole-board models of anxiety, diazepam (0.75 mg/kg) and psychollatine (7.5 and 15 mg/kg) showed anxiolytic-like effect at doses that do not increase sleeping time nor alter spontaneous locomotor activity. The anxiolytic effect of psychollatine was prevented by prior administration of ritanserin, but not of picrotoxin, indicating that 5-HT2 but not GABA receptors are implicated. In the forced swimming model of depression, psychollatine (3 and 7.5 mg/kg) effects were comparable to the antidepressants imipramine (15 mg/kg) and fluoxetine (20 mg/kg). Psychollatine suppressed oxotremorine-induced tremors in all doses. In the step-down learning paradigm, diazepam (0.85 mg/kg), MK-801 (0.15 mg/kg), and psychollatine 100 mg/kg impaired the acquisition of learning and memory consolidation, without interfering with retrieval. It is concluded that the effects of psychollatine at the central nervous system involve serotonergic 5HT2(A/C) receptors.

Behavioural and biochemical studies with the benzamide sulpiride in rats.

We have studied the effects of the benzamide, sulpiride, on dopamine transmission using a functional approach combining brain dialysis experiments with behavioural studies utilising rotational and holeboard models. In the 6-OH-dopamine-rotational model, both apomorphine and pergolide induced a dose-dependent contralateral rotation. However, sulpiride blocks very effectively the pergolide responses whilst it inhibits poorly the apomorphine rotation. Further studies using the same model suggest different receptor mechanisms distinctly distributed in the striata of rats and involving different efferent pathways. A dialysis tube was implanted into the left striatum of rats in order to study changes in dopamine release after influencing dopamine autoreceptors. Apomorphine produced a decrease of dopamine release which was reversed by sulpiride. The dopamine autoreceptor regulation of exploratory behaviour has been studied using an automatic holeboard device. Apomorphine and pergolide inhibited locomotion in an dose-dependent manner. This inhibition was selectively reversed by sulpiride but not by cis-flupenthixol. The dialysis provided also another possibility to study the functional regulation of DA systems. It has been suggested that sulpiride most effectively blocks the dopamine receptors localized presynaptically on cortico-striatal glutamate afferent neurons. We have compared the effects of cis-flupenthixol and sulpiride on glutamate and GABA release as measured by dialysis in the striata of rats. We found no clearcut effect after cis-flupenthixol, while sulpiride caused a significant change in glutamate release.