Anxiolytic-Like Effect of baicalin and its additivity with other anxiolytics

Baicalin, a naturally occurring flavonoid, was previously reported to exert anxiolytic-like effects in the Vogel conflict test. In the present study, the anxiolytic effects of baicalin alone and in combination with other anxiolytics were tested in mice using the elevated plus-maze (EPM). Baicalin treatment (7.5 - 30 mg/kg) significantly increased entries into and time spent in open arms, indicative of an anxiolytic-like effect. Motor-depressive and myorelaxant side effects commonly associated with anxiolytics were not observed with baicalin at effective anxiolytic doses in the hole-board and horizontal wire tests, respectively. Co-administration of baicalin (3.75 mg/kg) with dl-tetrahydropalmatine ( dl-THP; 0.25 mg/kg), an anxiolytic-hypnotic alkaloid, both at sub-effective doses, induced an additive effect resulting in considerable anxiolysis. Similarly, an additive anxiolytic-like effect was observed with baicalin (3.75 mg/kg) and diazepam (DZ; 0.5 mg/kg). Results obtained from this study demonstrate the potential of baicalin as a candidate anxiolytic and its possible application in multidrug therapy. Abbreviations. BZS:benzodiazepine-binding site EPM:elevated plus-maze DZ:diazepam GABA (A):type A gamma-aminobutyric acid dl-THP: dl-tetrahydropalmatine.     

Agmatine and a cannabinoid agonist, WIN 55212-2, interact to produce a hypothermic synergy

Agmatine blocks morphine withdrawal symptoms and enhances morphine analgesia in rats. Yet, the role of agmatine in the pharmacological effects of other abused drugs has not been investigated. The present study investigates the effect of agmatine administration on the hypothermic response to cannabinoids. Hypothermia is an effective endpoint because cannabinoid agonists produce a rapid, reproducible, and significant decrease in body temperature that is abolished by cannabinoid CB(1) receptor antagonists. WIN 55212-2, a cannabinoid agonist, was administered to rats by itself and with agmatine. WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.) caused a significant hypothermia. Agmatine (10, 25 and 50 mg/kg, i.p.) was ineffective. For combined administration, agmatine (50 mg/kg, i.p.) enhanced the hypothermic effect of WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.). The enhancement was strongly synergistic, indicated by a 2.7-fold increase in the relative potency of WIN 55212-2. The central administration of agmatine (25 and 50 mug/rat, i.c.v.) significantly increased the hypothermic effect of WIN 55212-2 (2.5 mg/kg, i.m.). This indicates that agmatine acts through a central mechanism to augment cannabinoid-evoked hypothermia. Idazoxan (2 mg/kg, i.p.), an imidazoline antagonist, blocked the enhancement by agmatine, thus suggesting that imidazoline receptor activation is required for agmatine to enhance cannabinoid-evoked hypothermia. The present data reveal that agmatine and a cannabinoid agonist interact to produce a hypothermic synergy in rats. These results show that agmatine acts in the brain and via imidazoline receptors to enhance cannabinoid-evoked hypothermia.     

Antitussive effect of WIN 55212-2, a cannabinoid receptor agonist

Several lines of evidence indicate that the opioid and cannabinoid systems produce synergistic interactions. The present study examined the opioid receptors involved in the antitussive effect of WIN 55212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate), a high-affinity cannabinoid receptor agonist, in mice. WIN 55212-2, at doses of 0.3-3 mg/kg ip, produced a dose-dependent antitussive effect. This antitussive effect of WIN 55212-2 was antagonized by pretreatment with either methysergide (3 mg/kg ip), a 5-HT receptor antagonist, or naloxone (1 mg/kg ip), an opioid receptor antagonist. Furthermore, pretreatment with N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A, 3 mg/kg ip), a cannabinoid CB(1) receptor antagonist, also significantly reduced the antitussive effect of WIN 55212-2. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine (40 mg/kg sc) significantly reduced the antitussive effect of WIN 55212-2. However, pretreatment with nor-binaltorphimine (20 mg/kg sc), a kappa-opioid receptor antagonist, did not affect the antitussive effect of WIN 55212-2. Pretreatment with naloxonazine (35 mg/kg sc), a mu(1)-opioid receptor antagonist, also did not affect the antitussive effect of WIN 55212-2. These results indicate that the antitussive effect of WIN 55212-2 is mediated by the activation of cannabinoid CB(1) receptors and mu(2) (naloxonazine-insensitive)-opioid receptors, but not mu(1) (naloxonazine-sensitive)- or kappa-opioid receptors.     

Antagonism between the anti-inflammatory activity of the cannabinoid WIN 55212-2 and SR 141716A

The CB1/CB2 receptor agonist WIN 55212-2 (0.75 mg/kg, i.v.) caused a significant reduction in neurogenic plasma extravasation induced by electrical stimulation of the saphenous nerve in anesthetized rats; WIN 55212-2 at 2.5-10 mg/kg, s.c., also produced a significant reduction in the carrageenan-induced paw edema in conscious rats. The selective CB1 antagonist SR 141716A (0.075-0.75 mg/kg i.v.) antagonized the WIN 55212-2 effects in the plasma extravasation model and antagonized the WIN 55212-2 (2.5 mg/kg, s.c.)-induced decreases in rectal temperature and increases in tail-flick latencies. However, SR 141716A (10 mg/kg, p.o.) failed to antagonize the effects of Win 55212-2 (2.5 mg/kg, s.c.) in the carrageenan model, suggesting that cannabinoid receptors found in the periphery may be able to modulate inflammatory processes in rats.     

Agmatine enhances cannabinoid action in the hot-plate assay of thermal nociception

Agmatine–cannabinoid interactions are supported by the close association between cannabinoid CB₁ receptors and agmatine immunoreactive neurons and evidence that shared brain mechanisms underlie the pharmacological effects of agmatine and cannabinoid agonists. In the present study, we used the hot-plate assay of thermal nociception to determine if agmatine alters cannabinoid action through activation of imidazoline sites and/or alpha₂-adrenoceptors. WIN 55212-2 (1, 2 or 3 mg/kg, i.p.) or CP55,940 (1, 2 or 3 mg/kg, i.p.) administration increased hot-plate response latency. Agmatine (50 or 100 mg/kg, i.p.) was ineffective. Administration of agmatine (50 mg/kg, i.p.) with WIN 55212-2 (1, 2 or 3 mg/kg, i.p.) or CP55,940 (1, 2 or 3 mg/kg, i.p.) produced response-latency enhancement. Regression analysis indicated that agmatine increased the potency of WIN 55212-2 and CP55,940 by 3- and 4.4-fold, respectively, indicating synergy for both drug interactions. Idazoxan, a mixed imidazoline site/alpha₂-adrenoceptor antagonist, but not yohimbine (5 mg/kg, i.p.), a selective alphia₂-adrenoceptor antagonist, blocked response-latency enhancement produced by a combination of WIN 55212-2 (2 mg/kg) and agmatine. Response-latency enhancement produced by WIN 55212-2 (2 mg/kg) was blocked by SR 141716A (5 mg/kg, i.p.), a cannabinoid CB₁ receptor antagonist; attenuated by idazoxan (2 and 5 mg/kg); and not affected by yohimbine (5 mg/kg). These results demonstrate a synergistic interaction between agmatine and cannabinoid agonists and suggest that agmatine administration enhances cannabinoid action in vivo.     

Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety

Aim:

The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT₃) receptor antagonist in experimental mouse models of anxiety.

Materials and Methods:

The anxiolytic activity of “6g” (1 and 2 mg/kg, intraperitoneally [i.p.]) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus maze (EPM), light-dark (L&D) box, hole board (HB), and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. None of the tested dose of “6g” affects the base line locomotion.

Results:

The new chemical entity “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the percentage of time spent and number of entries in open arm in the EPM test. In the L&D test compound “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the total time spent in light compartment as well as number of transitions from one compartment to other. Compound “6g” (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly (P < 0.05) increased number of head dips, whereas significantly (P < 0.05) decreased the head dipping latency in HB test as compared to vehicle control group. In addition, 6g (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores (square crossed) in OFT and there was no significant effect of 6g (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) on rearing scores.

Conclusion:

In conclusion, these findings indicated that compound “6g” exhibited an anxiolytic-like effect in animal models of anxiety.KEY WORDS: Anxiety, elevated plus maze, hole-board, 5-HT₃ receptor antagonist, open field test     

Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (Δ(9)-tetrahydrocannabinol) discrimination for rats

We examined four different cannabinergic aminoalkylindole ligands, including one drug (AM678=JWH018) found in herbal 'Spice' concoctions, for their ability to substitute for Δ(9)-tetrahydrocannabinol (THC), and the ability of the cannabinoid receptor 1-selective antagonist/inverse agonist rimonabant to block the substitution, 30 and 90 min after intraperitoneal injection. Rats trained to discriminate the effects of vehicle from those produced by 3 mg/kg of THC were used. The order of potency was: AM5983≥AM678>AM2233>WIN55212-2 at both test intervals. AM5983 and AM678 appeared eight times more potent than THC, followed by AM2233 (about twice as potent as THC), and WIN55212-2 approximately THC at the 30-min test interval. The aminoalkylindoles showed reduced potency (i.e. an increased ED50 value) at the longer injection-to-test interval of 90 min compared with testing at 30 min. The rightward shifts by coadministration of rimonabant were approximately 8-fold to 12-fold for AM5983 and AM678, compared with an approximately 3-fold rightward shift for the WIN55212-2 curve. AM2233 (1.8 mg/kg) substitution was also blocked by 1 mg/kg of rimonabant. In conclusion, AM5983 and AM678=JWH018 are potent cannabimimetics derived from an aminoalkylindole template. WIN55212-2 seemed to interact differently with rimonabant, compared with either AM5983 or AM678, indicating potential differences in the mechanism(s) of action among cannabinergic aminoalkylindoles.     

Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats

This study investigated the effect of Withania somnifera Dunal (WS) root extract and diazepam in social isolation induced behavior such as anxiety and depression in rats. Rats were isolated for 6 weeks and the assessment of changed behavior were done on elevated plus maze (EPM) and forced swim test (FST). Isolation reared rats spent less time into the open arms on EPM and significantly increased immobility time in FST compared to group housed rats. WS (100, 200 or 500 mg/kg, oral) and diazepam (1 or 2 mg/kg, ip) dose dependently increased the time spent and entries into the open arms on EPM test and showed the anxiolytic activity. Subeffective dose of WS (50 mg/kg, oral) potentiated the anxiolytic action of diazepam (0.5, 1 or 2 mg/kg, ip). WS (100, 200 or 500 mg/kg, oral) also reduced the immobility time in FST, thus showed antidepressant effect in both group housed and social isolates. The investigations support the use of WS as a mood stabilizer in socially isolation behavior in Ayurveda.     

Agmatine enhances cannabinoid action in the hot-plate assay of thermal nociception

Agmatine–cannabinoid interactions are supported by the close association between cannabinoid CB₁ receptors and agmatine immunoreactive neurons and evidence that shared brain mechanisms underlie the pharmacological effects of agmatine and cannabinoid agonists. In the present study, we used the hot-plate assay of thermal nociception to determine if agmatine alters cannabinoid action through activation of imidazoline sites and/or alpha₂-adrenoceptors. WIN 55212-2 (1, 2 or 3 mg/kg, i.p.) or CP55,940 (1, 2 or 3 mg/kg, i.p.) administration increased hot-plate response latency. Agmatine (50 or 100 mg/kg, i.p.) was ineffective. Administration of agmatine (50 mg/kg, i.p.) with WIN 55212-2 (1, 2 or 3 mg/kg, i.p.) or CP55,940 (1, 2 or 3 mg/kg, i.p.) produced response-latency enhancement. Regression analysis indicated that agmatine increased the potency of WIN 55212-2 and CP55,940 by 3- and 4.4-fold, respectively, indicating synergy for both drug interactions. Idazoxan, a mixed imidazoline site/alpha₂-adrenoceptor antagonist, but not yohimbine (5 mg/kg, i.p.), a selective alphia₂-adrenoceptor antagonist, blocked response-latency enhancement produced by a combination of WIN 55212-2 (2 mg/kg) and agmatine. Response-latency enhancement produced by WIN 55212-2 (2 mg/kg) was blocked by SR 141716A (5 mg/kg, i.p.), a cannabinoid CB₁ receptor antagonist; attenuated by idazoxan (2 and 5 mg/kg); and not affected by yohimbine (5 mg/kg). These results demonstrate a synergistic interaction between agmatine and cannabinoid agonists and suggest that agmatine administration enhances cannabinoid action in vivo.     

Anxiety-like behavior induced by histaminergic agents can be prevented by cannabinoidergic WIN55,212-2 injected into the dorsal hippocampus in mice

In the present study, we investigate the effects of the histaminergic system and cannabinoid receptor agents on anxiety-related behaviors and their interactions using the hole-board test on mice. Bilateral intra-CA1 administration of the CB1/CB2 receptor agonist, WIN55, 212-2 (0.1-0.5 µg/mouse) did not modify exploratory behaviors in mice. On the other hand, intra-CA1 administration of CB1 receptor antagonist, AM251 (25 and 50 ng/mouse) or histamine, pyrilamine and ranitidine (5-10 µg/mouse) decreased the amount of head-dipping and increased the first head-dip, suggesting an anxiogenic-like response. Furthermore, our present data indicated that the co-administration of WIN55, 212-2 (0.25 µg/mouse) with histaminergic agents, decreased the anxiogenic-like response of an effective dose (5 µg/mouse) of histamine and pyrilamine, but not that of ranitidine. In addition, the results demonstrated that co-administration of an ineffective dose of AM251 (15 ng/mouse) with histaminergic drugs did not alter the response induced by an ineffective dose (3.75 µg/mouse) of either histamine or pyrilamine and ranitidine. In all experiments and doses, locomotor activity and other exploratory behaviors were not significantly changed. In conclusion, our results showed that there is a chance of partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiogenic/anxiolytic-like behaviors in hole-board test.     

Evaluation of the Anticonvulsant and Anxiolytic Potentials of Methyl Jasmonate in Mice

Methyl jasmonate (MJ) is one of the most well-studied plant stress hormones belonging to the jasmonate family. Previous studies have shown that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting potential benefits in disorders associated with hyperactivity of the brain. This study was carried out to evaluate whether MJ has anticonvulsant and anxiolytic properties in mice. The anticonvulsant effect was assessed based on the prevention of tonic-clonic seizures induced by chemoconvulsant agents in mice. The anxiolytic property was evaluated utilizing the elevated plus maze (EPM) and light/dark transition paradigms. The effect of MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received intraperitoneal (i.p.) injections of MJ 30 min before the tests were carried out and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50–400 mg/kg) did not protect the mice against tonic-clonic convulsions induced by picrotoxin (10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200, and 400 mg/kg) offered 20, 60, and 100% protection against pentylenetetrazole (100 mg/kg, i.p.)-induced convulsions. In a similar manner to diazepam (2 mg/kg), MJ (400 mg/kg) produced a marked sedative effect as shown by decreases in the number of lines crossed and the duration of ambulation in the open field test. In contrast to diazepam (2 mg/kg), MJ (5–50 mg/kg) did not show anxiolytic effects in the EPM and light/dark transition paradigms. These findings suggest that methyl jasmonate at high doses possessed anticonvulsant properties in the pentylenetetrazole animal model of epilepsy, but did not produce anxiolytic activity in mice.     

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.     

Increased sensitivity of adolescent spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder, to the locomotor stimulation induced by the cannabinoid receptor agonist WIN 55,212-2

Converging evidence points to adolescence as a critical period for the onset of a wide range of neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD) and drug abuse. Spontaneously hypertensive rats (SHR) are generally considered to be a suitable genetic model for the study of ADHD, since they display hyperactivity, impulsivity, poorly sustained attention, cognitive deficits and increased novelty seeking. Despite the high prevalence of ADHD among adolescents, studies using SHR have mainly been performed on adult animals. The aim of the present study was to evaluate the effect of acute intraperitoneal (i.p.) administration of the cannabinoid receptor agonist WIN 55,212-2 (0.25-2.5 mg/kg) on locomotor activity and anxiety-like behavior in male adolescent and adult SHR and Wistar rats using the open field and elevated plus-maze tests. WIN 55,212-2 at doses of 0.25 and 1.25 mg/kg (i.p.) selectively promoted locomotor stimulation in adolescent SHR in the open field, but not in adult SHR or Wistar rats (regardless of age). The effect of WIN 55,212-2 (0.25 mg/kg, i.p.) on locomotion of adolescent SHR was reversed by pretreatment with the selective cannabinoid CB1 receptor antagonist AM 251 (0.25 mg/kg, i.p.). Moreover, although the present doses of WIN 55,212-2 had no effect on anxiety-related behaviors in any of the animal groups evaluated in the open field (central locomotion) or elevated plus-maze (time and entries in open arms), the highest dose of WIN 55,212-2 tested (2.5 mg/kg, i.p.) significantly decreased the number of closed-arm entries (an index of locomotor activity) of adolescent rats of both the Wistar and SHR strains in the elevated plus-maze. The present results indicate strain- and age-related effects of cannabinoids on locomotor activity in rats, extending the notion that adolescence and ADHD represent risk factors for the increased sensitivity to the effects of drugs.     

Effects of buspirone on antinociceptive and behaviourial responses to the elevated plus-maze in mice

Brief exposure to an elevated plus-maze (EPM) induces antinociception in male mice, a reaction that is not blocked by opiate receptor manipulations but which is completely inhibited by the benzodiazepine receptor agonist, diazepam. The present study examined the effects of a non-benzodiazepine anxiolytic, buspirone, on EPM antinociception and behaviour. EPM antinociception was completely abolished by 10mg/kg buspirone but was largely unaffected by lower doses (0.1-1.0mg/kg) of the compound. Behaviourally, 1-10mg/kg buspirone produced changes indicative of anxiety reduction, although the high dose anxiolytic profile was at least partially compromised by a general reduction in behaviour. Data are discussed in relation to the proposal that anxiety may be a critical factor in non-opioid forms of adaptive pain inhibition.     

Diazepam-induced release of behavior in an extinction procedure: its reversal by Ro 15-1788

The effects of the benzodiazepine receptor antagonist Ro 15-1788, an imidazobenzodiazepine derivative, were studied with respect to three pharmacological activities exerted by diazepam in rats. Two of these, release of shock-induced suppression of drinking and attenuation of non-reward-induced cessation of responding for food, reflect the anxiolytic property of benzodiazepines. The amnesic-like effect of diazepam was also investigated. Ro 15-1788 (in doses ranging from 4 to 16 mg/kg p.o.) completely reversed diazepam (2 mg/kg)-induced release of behavior in both punishment and non-reward procedures. In contrast, Ro 15-1788 reduced but did not completely abolish diazepam-induced amnesia. These data suggest that the anticonflict and anti-frustration effects of benzodiazepines probably involve similar receptor types which nevertheless differ from those chiefly implicated in the amnesic-like activity of benzodiazepines.     

Effect of GB-115 dipeptide on anxiety in rats with model benzodiazepine withdrawal syndrome

The effects of GB-115 dipeptide, a retroanalog of endogenous CCK-4, on the behavioral indices in "elevated plus maze" (EPM) test and on the content of biogenic amines in the brain structures after discontinuation of a chronic administration of benzodiazepine (BZ) derivatives phenazepam (2.0 mg/kg, i.p.) and diazepam (4.0 mg/kg, i.p.) have been studied in outbred and inbred MR/MNRA rats. It is established that, in 24-48 h following BZ withdrawal, GB-115 dipeptide administered in doses of 0.1 and 0.5 mg/kg, i.p., produced an anxiolytic effect in all animals, which was manifested by increasing the stay time and number of entries in EPM. In the striatum of outbred rats, GB-115 increased DOPAC (+25%) and DA (+31.6%) levels that were decreased during diazepam withdrawal syndrome. The obtained results showed the GB-115 efficiency in attenuating the anxiety caused by BZ withdrawal.     

Effects of cannabinoids on the anxiety-like response in mice

Several pieces of anatomical, biochemical and pharmacological evidence indicate that the endocannabinoid system via CB1 receptors is implicated in the control of emotional behavior. However, previous studies have reported unclear and contradictory results concerning the role of cannabinoids in anxiety. The aim of the present study was to examine the influence of the cannabinoid agonist WIN 55,212-2 (1 and 5 mg/kg), the CB1 antagonist AM 281 (1, 2 and 4 mg/kg), the inhibitor of anandamide hydrolysis AACOCF3 (1 and 4 mg/kg) and the inhibitor of anandamide transporter AM404 (1 and 4 mg/kg) on the anxiety-like response in mice in the light/dark box test. WIN 55,212-2 (5 mg/kg) induced the anxiogenic-like effect accompanied by motor inhibition, AACOCF3 (4 mg/kg) induced the selective anxiolytic-like effect, whereas AM404 and AM281 were without effect. Pretreatment with AM281 (2 mg/kg) blocked the anxiogenic-like and sedative responses induced by WIN 55, 212-2, as well as the anxiolytic-like effect of AACOCF3. These results support the hypothesis that the endocannabinoid system is involved in the regulation of anxiety-like behavior, and also suggest that the inhibitors of anandamide hydrolysis might be potential anxiolytic drugs.     

Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments

Context In a previous study, it has been shown that ellagic acid (EA), a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms.

Objective The present study was conducted to assess the potential of EA as a memory enhancer.

Materials and methods The elevated plus maze (EPM) and passive avoidance (PA) paradigm were used to evaluate learning and memory parameters. Three doses (10, 30 and 100?mg/kg, i.p.) of EA were administered to animals. Memory impairment was induced by scopolamine treatment (0.4?mg/kg, i.p.) and/or diazepam (1?mg/kg, i.p.). Acquisition trials were carried out 30?min after scopolamine treatment and retention trials were performed for 5?min 24?h after the acquisition trials.

Results EA at doses 30 and 100?mg/kg significantly reversed the amnesia induced by scopolamine (0.4?mg/kg, i.p.) in the EPM and PA tests in mice. Also, EA at doses 30 and 100?mg/kg significantly antagonized the amnesia induced by diazepam (1?mg/kg, i.p.) in EPM test in rats. Moreover, chronic administration of EA at dose 30?mg/kg ameliorated the memory deficit induced by diazepam (1?mg/kg, i.p.) in rats.

Discussion and conclusion This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals’ locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons.     

Anxiolytic-like effect of asiaticoside in mice

The putative anxiolytic activity of asiaticoside was examined in male mice by using a number of experimental paradigms of anxiety, with diazepam being as a positive anxiolytic control. In the elevated plus-maze test, diazepam (1 and 2 mg/kg) or asiaticoside (5 or 10 mg/kg) increased the percentage of entries into open arms and of time spent on open arms. In the light/dark test, as with 1 mg/kg diazepam, asiaticoside (10 and 20 mg/kg) increased the time spent in the light area and the movement in the light area without altering the total locomotor activity of the animals. In the hole-board test, asiaticoside at 10 mg/kg significantly increased head-dipping counts and duration as well as diazepam (0.3 mg/kg). Thus, these findings indicated that asiaticoside exhibited an anxiolytic-like effect. Further studies will be required to assess the generality of present findings to other species and behavioural paradigms.     

Effects of taurine on rat behaviors in three anxiety models

In our previous studies using an elevated plus-maze test in mice, taurine was shown to present an anxiolytic-like effect after single and repeated administration. The aim of the present study was to investigate the anxiolytic and behavioral effects of taurine on rats in the open field, hole-board, and social interaction test compared to the positive control diazepam. Taurine (14, 42, and 126 mg/kg, i.p.) was administered 30 min before the tests. In the social interaction and hole-board tests, taurine (42 mg/kg) significantly increased social interaction time and the number and duration of head-dipping. In the open field test, taurine (126 mg/kg, i.p.) presented anxiolytic-like effects by increasing the number of center entries, time spent in the central area and the anti-thigmotactic score while having no effect on the locomotor activity. Results from these experiments suggest that taurine produces an anxiolytic-like effect in these animal models and may act as a modulator or anti-anxiety agent in the central nervous system.