The Influence Of Kolanut (Cola Nitida) On Exploratory Behaviour In Rats

The effect of oral administration of an aqueous extract of kolanut ( Cola nitida ) on exploration of a Y-maze was investigated in rats. The number of entries made into all the arms of the maze and the frequency of rearing following administration of the extract was determined over 20 min, and repeated 24 h later without administration of the extract. Both the extract (400 and 800 mg/kg) and caffeine (15 mg/kg) caused significant increases in the number of entries, but reduced the frequency of rearing. The extract did not significantly reduce the number of entries after 24 h. It is suggested that kolanut stimulates exploratory locomotor activity due to its caffeine content, but does not enhance habituation.     

The role of the benzodiazepine receptor in mediating long-lasting anticonvulsant effects and the late-appearing reductions in motor activity and exploration

The number of head-dips, the time spent head-dipping, the number of rears and the locomotor activity of mice placed in a holeboard was reduced by lorazepam (0.25 mg/kg) 1 and 1.5 h after oral administration and these reductions were reversed by the benzodiazepine antagonist flumazenil (1 mg/kg). Activity returned to control levels at 3 and 4.5 h for head-dipping, and between 3 and 12 h for rearing and locomotor activity. However, significant late-appearing reductions were found for the number of head-dips and the time spent head-dipping (6 h) and rearing and locomotor activity (15 h) and these decreases could not be reversed by flumazenil. Similar results were found after oral administration of oxazepam (7 mg/kg). Oxazepam reduced the number of head-dips and time spent head-dipping at 1, 1.5 and 3 h and these reductions were reversed by flumazenil (1 mg/kg). Head-dipping activity returned to normal at 4.5 h. Significant reductions were also found for both measures at 1, 6 and 7.5 h and these late reductions could not be reversed by flumazenil. This suggests that the late-appearing reductions in holeboard behaviours, resulting from lorazepam or oxazepam administration to mice, is not mediated by the benzodiazepine receptor. This conclusion was supported by the results from in vivo binding, which showed no change in the % receptor occupancy 3–15 h after administration of lorazepam or oxazepam. In contrast to the holeboard behaviours, the anticonvulsant effects of the two drugs showed good correlations with receptor occupancy. The anticonvulsant effect of oxazepam (7 mg/kg) significantly decreased 1–3 h after oral administration, but thereafter a steady anticonvulsant effect was retained for up to 24 h. The anticonvulsant effect of lorazepam (0.25 mg/kg) also significantly decreased 1–3 h after administration, and thereafter remained steady for up to 15 h. At all the time-points tested, oxazepam (7 mg/kg) had a significantly greater anticonvulsant effect than lorazepam (0.25 mg/kg). This was mirrored by higher percentage receptor occupancies in cortex, hippocampus and cerebellum, from 3 to 15 h after administration.     

Combination of adenosine A1 and A2A receptor blocking agents induces caffeine-like locomotor stimulation in mice.

The spontaneous locomotor activity of C57BL/6J mice was examined, using an automated detection system based on infra-red beams, after administration of caffeine (3-30 mg/kg, i.p.), the adenosine A(2A) receptor selective antagonist SCH 58261 (0.312-2.5 mg/kg, i.p.) and the A(1) selective antagonist DPCPX (1.25-5 mg/kg, i.p.). SCH 58261 failed to influence motor activity in mice habituated to the test environment. DPCPX produced a small increase in motility and locomotion (significant at the dose of 5.0 mg/kg), much weaker than that produced by caffeine. Combined administration of DPCPX (1.2 mg/kg, i.p.) and SCH 58261 (1.2 mg/kg, i.p.) produced stimulation of motility and locomotion comparable with the effect of caffeine (15 mg/kg, i.p.). In contrast to motility and locomotion, rearing counts were not significantly influenced by DPCPX, SCH 58261, their combination, or by caffeine. Caffeine (15 mg/kg, i.p.) caused an increase in NGFI-A mRNA (an immediate early gene was chosen as an index of neuronal activation) in the piriform cortex 4 h after injection. This effect was reproduced by the combination of A(1) and A(2A) receptor antagonist. It is hypothesised that the stimulatory effect of low doses of caffeine in C57BL/6J mice is due to concomitant blockade of both A(1) and A(2A) adenosine receptors.     

Caffeine withdrawal syndrome in social interaction test in mice: effects of the NMDA receptor channel blockers, memantine and neramexane

Antagonists acting at N-methyl-D-aspartate (NMDA) receptors have been demonstrated repeatedly to attenuate the expression of drug and alcohol withdrawal syndromes. The present study aimed to evaluate the effects of NMDA receptor blockade on the expression of behavioural signs of caffeine withdrawal syndrome, assessed using the social interaction paradigm. Adult male Swiss mice were treated with increasing doses of caffeine (40-100 mg/kg, i.p., twice daily) for 8 days. Twenty-four hours after the last injection of caffeine, there were significant increases in duration and frequency of defensive behaviours, as well as decreased locomotor activity. These changes faded within 72 hours. Pretreatment with a single dose of caffeine (1 mg/kg; 24 h after the end of repeated caffeine administration and 30 min prior to the test) completely reversed these withdrawal-related changes. Separate groups of mice were treated i.p. with different doses of memantine (1, 3 or 10 mg/kg) or neramexane (MRZ 2/579; 1, 3 or 10 mg/kg) 24 h after the last caffeine injection. Both compounds dose-dependently reduced the expression of defensive behaviours while increasing motor activity. These data suggest that NMDA receptor blockade may counteract the acute behavioural effects of caffeine withdrawal.     

Caffeine and nicotine: differential effects on ambulation, rearing and wheelrunning

Male Sprague Dawley rats were tested for open field ambulation and rearing, and for wheelrunning, following repeated injections of either caffeine or nicotine, given according to a Latin Square design. Caffeine enhanced ambulation and rearing at 5 and 15 mg/kg, IP, and increased wheelrunning with 15 and 45 mg/kg. Nicotine (0.63 mg/kg) also enhanced ambulation, but not rearing, and depressed wheelrunning during the first 20 min of testing. Caffeine's enhancement of wheelrunning was not significant during the first two drug administrations. Results suggest that caffeine and nicotine affect activity via different neuropharmacological mechanisms. Previous experience with these drugs may modulate animals' reactivity to them.     

Suppressant effect of REM sleep deprivation on neophobia in normal rats and in rats with selective DSP-4 induced damage of locus coeruleus neurons

The influence of REM sleep deprivation (REMD) on open field behavior of normal and locus coeruleus (LC)-damaged animals was investigated under the assumption that REMD suppresses neophobia in rats. REMD (for 24 or 72 hr, water tank technique) produced marked changes in behavior of rats encountering a novel object (white cube) in the center of the open field. REMD induced an increase in activity of treated rats; latency to the object approach was shorter, the number of center entries, time spent in object exploration, frequency of ambulation and rearing were significantly higher than in controls, also defecation was nearly abolished. LC-damage (using DSP-4, a selective central noradrenergic neurotoxin) induced neophobic-like reactions manifested by significantly prolonged latency, tendency to decreased object exploration, center entries and reduction of ambulation and rearing. This "neophobic" behavior of DSP-4 rats was counteracted by REMD as well as by subchronic, but not acute treatment, with antidepressant oxaprotiline (2 X daily for 8 days, 10 mg/kg, IP). The results provide strong support for antineophobic activity of REMD. In addition, they indicate possible similarity of REMD and subchronic oxaprotiline action on neophobia-like behavior in rats with damaged LC-neurons.     

Investigation of the effects of concomitant caffeine administration on the metabolic disposition of pyrazinamide in rats

The utility of pyrazinamide (PZA) in the short-course antituberculous treatment is well established. All available data support the idea that the PZA metabolite pyrazinoic acid (PA) is the active compound against M. tuberculosis. This situation warranted a deeper investigation of possible interactions with respect to its metabolic disposition. Caffeine, which is widely used as a drug and is a common constituent of most diets, shares with PZA the same metabolic enzyme, xanthine oxidase (XO). This study investigated if, and in what manner, concomitant administration of caffeine affects PZA metabolism. PZA and caffeine, in various doses (PZA=50 or 100 mg kg(-1) and caffeine= 0, 50, 100, and 150 mg kg(-1)), were administered to female Sprague-Dawley rats. PZA and its three main metabolites were quantified in 24 h urine samples by reversed phase-HPLC Concomitant administration of 100 mg kg(-1) caffeine and 50 mg kg(-1) PZA increased from the excretion (p<0.05) of the most water-soluble and the least toxic PZA metabolite 5-hydroxypyrazinoic acid (5-OH-PA) from 66.18+/-10.87 to 94.56+/-8.65 micromol/24 h. This effect was more pronounced when 100 mg kg(-1) of PZA was administered increasing excretion of 5-OH-PA from 113.28+/-70 to 173.23+/-17.82 micromol/24 h. These results show that the metabolic disposition of PZA is affected by concomitant caffeine intake.     

Imipramine normalizes naturally-occurring and drug-induced differences in the exploratory activity of rats.

1 Exploratory activity of female hooded rats was measured in a Y maze on two occasions, 1 week apart. Locomotion (maze arm entries), rearing, and head-dipping into pots were scored for 5 min at each trial. 2 In control rats, differences between individuals in the amount of locomotion and rearing were consistent, as shown by significant test-retest correlations (r = +0.55, and +0.83 respectively). There was no correlation between head-dipping scores obtained in the two tests. 3 Imipramine (Imip) pretreatment before the second trial (10 mg/kg i.p on the 3 preceding days, and 2.5 mg/kg 1 h before) abolished these correlations. The scatter of the scores about the mean was also reduced by Imip, but there was no significant change in mean scores. Thus Imip appeared to have a 'normalizing' effect on locomotion and rears: after pretreatment, scores tended to be more uniform, and no longer reflected naturally-occurring individual differences. 4 Imip abolished the changes in exploratory activity produced by drugs which alter brain 5-hydroxytryptamine metabolism: p-chlorophenylalanine (100 mg/kg 24 h before testing) increased and DL-5-hydroxytryptophan (12.5 mg/kg 1 h before testing) decreased the fall in activity over the trial in saline-treated rats but not that in Imip-treated rats. In this case, Imip also produced an overall reduction in activity scores. 5 The normalizing effects of Imip on rat behaviour may be analogous to its therapeutic effects in human depressive disorders.     

Long-term diazepam treatment produces changes in cholecystokinin receptor binding in rat brain

This study examined the effect of chronic diazepam administration on central benzodiazepine and CCK-8 receptor binding in rat brain. After a two-week treatment with diazepam (5 mg/kg per day) tolerance developed towards the sedative but not towards the anxiolytic action of this drug as determined using elevated plus-maze and open field tests. The % entries the rats made onto open arms and % time the rats spent in open arms were markedly decreased 24 h after the last dose of diazepam, probably indicating withdrawal anxiety. There were no changes in [3H]flunitrazepam binding either 30 min or 24 h after the last diazepam dose. However, 30 min after the last diazepam administration the apparent number of sulphated [3H]CCK-8 binding sites was significantly increased in the primary olfactory cortex. Acute diazepam treatment (5 mg/kg) had no influence on [3H]flunitrazepam or sulphated [3H]CCK-8 binding in any brain region studied. Cessation of chronic diazepam treatment was followed after 24 h by an increase in the number of CCK-8 receptors in frontal cortex and hippocampus as compared to the vehicle group. These results demonstrate that certain alterations in CCK-8 receptor characteristics may be important in the anti-anxiety effect, tolerance, and withdrawal reaction reaction after benzodiazepine administration.     

Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love")

The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.     

Anxiogenic activity of Myristica fragrans seeds.

In the present study, the n-hexane extract of Myristica fragrans (MF) seeds, acetone-insoluble part of the n-hexane extract (AIMF) and trimyristin (TM) were assessed for their anxiogenic activity. The MF (10 and 30 mg/kg), AIMF (30, 100, and 300 mg/kg), and TM (10, 30, and 100 mg/kg) administered intraperitoneally exhibited anxiogenic activity in elevated plus-maze (EPM) paradigm. The open-field test and hole-board test were also used to assess anxiogenic activity of AIMF and TM. In the EPM test, MF, AIMF, and TM decreased the time spent by mice in the open arm and the entries in the open arm. Further, the effect of diazepam (1 mg/kg i.p.), serotonin 5-HT3 receptor antagonist, ondansetron (1 mg/kg i.p.), and 5-HT1A receptor agonist, buspirone (1 mg/kg i.p.), on the occupancy in open arm and entries in open arm was significantly reduced by TM. In the open-field test, AIMF as well as TM reduced the number of rearing and locomotion. Both TM and AIMF reduced the number of head pock in the hole-board test. Inhibition of anxiolytic activity of ondansetron (5-HT3 receptor antagonist), buspirone (5-HT1A receptor agonist), and diazepam [acting on gamma-aminobutyric acid (GABAA) receptor] suggests a nonspecific anxiogenic activity of TM and also a link between 5-HT and GABA systems in the anxiogenic activity of TM.     

Acute exposure to caffeine selectively disrupts context conditioning in rats

RATIONALE AND OBJECTIVE: Acute caffeine administration has both beneficial and adverse effects on learning and memory; however, the brain regions underlying these effects remain unclear. Several experiments were conducted to examine the effects of acutely administered caffeine on the acquisition and expression of hippocampal-dependent and hippocampal-independent forms of conditioned fear. METHODS: In the first experiment, caffeine (10, 20, or 30 mg/kg; IP) or vehicle was administered to rats 15 min prior to classical fear conditioning, which consisted of ten tone-shock pairings. Freezing to the conditioning context was measured 24 h later, whereas tone-elicited fear was measured 48 h later. A second experiment examined possible state-dependent effects of caffeine by administering caffeine (30 mg/kg) or vehicle 15 min before conditioning and before testing. RESULTS: Pretreatment of acute caffeine severely impaired the acquisition of context conditioning, a hippocampal-dependent task. Tone conditioning, a hippocampal-independent task, was only modestly and non-significantly affected by caffeine (4-21% suppression compared with controls). The disruption of context conditioning was dose-dependent: 10 mg/kg had little effect on context or tone conditioning, whereas doses of 20 and 30 mg/kg caffeine severely disrupted context conditioning (73-87% suppression). In two subsequent experiments, it was found that caffeine's selective disruption of context conditioning could not be attributed to the fact that it is a weaker form of learning than tone conditioning or to state-dependent learning. CONCLUSIONS: Considered together, these results suggest that acute administration of caffeine may preferentially disrupt the acquisition of hippocampal-dependent learning, including context conditioning.     

Tolerance to nicotine's effects in the elevated plus-maze and increased anxiety during withdrawal

In the elevated plus-maze test of anxiety, nicotine (0.1 mg/kg sc; 30 min after injection) had a significant anxiogenic effect, shown by specific decreases in the percentage of time spent on the open arms and in the percentage of open-arm entries. Tolerance developed to this anxiogenic effect after 7 days of nicotine treatment (0.1 mg/kg/day). Five minutes after an acute injection, nicotine (0.1 mg/kg) was ineffective, but after 7 days of treatment a significant anxiolytic effect, shown by specific increases in the percentage of time spent on the open arms and in the percentage of open-arm entries, emerged. After 14 days of nicotine treatment, tolerance developed to this anxiolytic effect. There was a complete dissociation between the effects of nicotine on the measures of anxiety, and on the locomotor activity as measured by closed-arm entries. No changes in closed-arm entries were found after acute administration of nicotine, but rats tested 30 min after their 7th injection made significantly fewer, and those tested 5 min after their 14th injection made significantly more, entries than their respective controls. Rats that were tested after 24 h withdrawal from six daily nicotine injections showed a significant anxiogenic effect. A low dose of nicotine (5 ng) injected into the dorsal hippocampus was without effect in vehicle pretreated rats, but it was able to reverse the anxiogenic effect found after 24 h of withdrawal from 6 days of nicotine treatment.     

Comparison of acute and chronic treatment of various serotonergic agents with those of diazepam and idazoxan in the rat elevated X-maze

The aim of this study was to use the elevated X-maze to compare acute and chronic treatments of a 5-HT_1A partial agonist, ipsapirone, a 5-HT₂ antagonist, ritanserin, and a 5-HT₃ antagonist, ondansetron, with those of established anxiolytic (diazepam) and anxiogenic (idazoxan) compounds. Acute diazepam (5 mg/kg IP) produced a significant increase in the percentage open:total entries and time and time spent in the end of the open arms (anxiolytic profile) on the elevated X-maze. Chronic treatment with diazepam (5 mg/kg IP twice daily for 14 days) still produced an anxiolytic profile which was not apparent 24 h after cessation of chronic treatment (withdrawal). In contrast, idazoxan given both acutely (0.25 mg/kg IP) and chronically (0.8 mg/kg/h at a flow rate of 5.5 µl/h for 14 days, via osmotic minipumps) resulted in a significant decrease in the percentage open:total entries and time and time spent in the end of the open arms (anxiogenic profile). Acute administration of ipsapirone had no effect on any of the behavioural parameters at doses of 0.01 and 1 mg/kg IP, while 0.1 mg/kg IP produced a significant anxiogenic profile. Chronic treatment with ipsapirone (0.01, 0.1 and 1 mg/kg IP twice daily for 14 days) had no significant effect on rat behaviour on the X-maze but 24 h after ending treatment, ipsapirone at the highest dose used (1 mg/kg) produced a significant anxiogenic profile which was absent when the animals were tested 7 days after cessation of treatment. Ritanserin (0.05 and 0.25 mg/kg IP) had no effect acutely on any of the parameters measured but chronic treatment (0.25 mg/kg IP, twice daily for 14 days) produced a significant anxiolytic effect which was still present 24 h but not 7 days after cessation of treatment. Acute ondansetron (0.01, 0.1 and 1 mg/kg IP) had no effect while chronic ondansetron (0.01 mg/kg IP, twice daily for 14 days) produced a significant anxiolytic profile which was not a result of handling during the chronic dosing schedule, an effect was not measureable 24 h after treatment ended. The results demonstrate that the X-maze can detect anxiolytic activity in non-benzodiazepine drugs, as ritanserin and ondansetron showed anxiolytic profiles but only after chronic treatment. In contrast, the X-maze failed to detect any anxiolytic activity with the 5-HT_1A partial agonist ipsapirone after either acute or chronic treatment.     

Effect of Morus alba L. (mulberry) leaves on anxiety in mice

Objective:

The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice.

Materials and Methods:

The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests.

Results:

The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant.

Conclusion:

The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.     

Formation of reactive metabolites of phenacetin in humans and rats

The metabolism of phenacetin to reactive intermediates in humans was estimated from the excretion of thio adducts in urine. N-Hydroxyphenacetin, a precursor of reactive metabolites, was also quantified. Following an oral dose of phenacetin (10 mg/kg) to humans, these metabolites in 24 h urine were: paracetamol-3-cysteine, 4.4% dose; paracetamol-3-mercapturate, 3.9%; 3-thiomethylparacetamol, 0.4%; N-hydroxyphenacetin, 0.5%. Rats showed a considerable increase in N-hydroxyphenacetin excretion after chronic dosing with phenacetin at high dosage (500 mg/kg) for one month. chronic dosing with a low dose (50 mg/kg) did not increase N-hydroxyphenacetin excretion, but a marked increase occurred on concomitant administration of aspirin and caffeine.     

Postsynaptic dopamine/adenosine interaction: II. Postsynaptic dopamine agonism and adenosine antagonism of methylxanthines in short-term reserpinized mice.

Caffeine and its first-stage metabolites (paraxanthine, theophylline and theobromine) caused a significant potentiation of the locomotor activity induced by bromocriptine, 5 mg/kg, in mice pretreated with reserpine, 5 mg/kg (4h prior to the start of motor activity recordings). None of these substances significantly enhanced locomotor activity in reserpinized mice when administered alone. The rank order of potency was caffeine greater than paraxanthine greater than theophylline greater than theobromine. A high dose of a D-2 antagonist (sulpiride 100 mg/kg) caused a marked inhibition of the locomotor activity induced by bromocriptine, 5 mg/kg, plus 25 mg/kg of caffeine, paraxanthine or theophylline. However, a high dose of a D-1 antagonist (SCH-23390 1 mg/kg) caused a significant decrease of the locomotor activity induced by bromocriptine 5 mg/kg, plus 25 mg/kg of caffeine or paraxanthine, but did not change the locomotor activity caused by bromocriptine, 5 mg/kg, plus theophylline 25 mg/kg. The inhibitory effect of 5'-(N-ethyl)carboxamido-adenosine (NECA), 0.025 mg/kg, on bromocriptine-induced locomotor activation in reserpinized mice was reversed by the simultaneous administration of 10, 25 and 50 mg/kg of caffeine, paraxanthine or theophylline. The rank order of potency for reversal was theophylline greater than paraxanthine = caffeine. We suggest that methylxanthines act postsynaptically by potentiating the effects of D-2 stimulation and that this potentiation can be produced by D-1 agonism (paraxanthine or caffeine) and by adenosine antagonism (theophylline, paraxanthine or caffeine), most probably involving A-2 receptors.     

Influence of kynurenine treatment on open-field activity, elevated plus-maze, avoidance behaviors and seizures in rats

In the present studies the effects of single and daily repeated injections of kynurenine were investigated in different behavioral tests in rats. In open-field behavior a single injection of kynurenine decreased rearing activity, while the effect was more pronounced after repeated injections. Similarly, in the elevated plus-maze, kynurenine attenuated the total number of entries in the four arms of the equipment, and after chronic treatment decreased the time spent in the open arms (control: 24%; kynurenine 100 mg/kg: 16%; kynurenine 200 mg/kg: 13%). Kynurenine did not influence the passive avoidance learning paradigm (learning session and avoidance latency) and the extinction of active avoidance response. Kynurenine slightly attenuated the kainic acid-induced wet dog shakes and forelimb clonic activity with rearing. These findings suggest that kynurenine (especially after repeated peripheral injections) inhibited several behavioral responses of the experimental animals. However, in one type of highly motivated experimental paradigm (fear from the foot shock), behavioral depression was not detectable.     

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

Objective:

To study the anxiolytic activity of methanol extract of Achyranthes aspera Linn (Amaranthaceae).

Materials and Methods:

Male Swiss albino mice were used. Methanolic extract of Achyranthes aspera (MEAA) was administered in the doses of 100, 300 and 600 mg/kg p.o. Hole board (HB), open field (OF), elevated plus maze (EPM) and light/dark exploration (LDE) tests were used for determination of anxiolytic activity.

Results:

The methanolic extract of Achyranthes aspera significantly increased the number and duration of head poking in HB test. The extract also significantly increased the time spent and the number of entries in open arm in EPM. In LDE test, the extract produced significant increase in time spent and number of crossings and decreased the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearing, assisted rearing and the squares crossed.

Conclusion:

In the present study, MEAA exhibited anxiolytic activity which might be attributed to its phyto-constituents viz. alkaloid, steroid and triterpenes. Since Achyranthes aspera is ubiquitous and abundantly grown, it could be a fairly economical therapeutic agent for management of anxiety disorders.KEY WORDS: Achyranthesaspera, anxiolytic activity, elevated plus maze, hole board, light/dark exploration, MEAA, open field     

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

Objective:

The aim of the present work was to evaluate the anxiolytic effect of an ethanolic extract of Nymphaea alba Linn. in mice.

Materials and Methods:

The elevated plus maze test (EPMT), light and dark test (L and DT) and open field test (OFT) were used to assess the anxiolytic activity of the ethanolic extract of N. alba Linn. in mice. In addition, aggressive behavior and motor coordination was also assessed by foot shock induced aggression test (FSIAT) and rota rod test (RRT). Diazepam 1 mg/kg served as a standard anxiolytic drug, administered orally.

Results:

The ethanolic extract of N. alba (100 and 200 mg/kg, p.o.) significantly increased the percentage of time spent and number of entries in open arm in EPMT. In L and DT, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. In FSIAT, N. alba extract attenuated aggressive behavior related to anxiolytic activity, such as number of vocalization, leaps, rearing, biting/attacks and facing each other in paired mice. Furthermore, the extract produced skeletal muscle relaxant effect assessed by RRT.

Conclusion:

The results of the present study suggest that an ethanolic extract of N. alba may possess anxiolytic activity and provide a scientific evidence for its traditional claim.