Antinociceptive activity of Tilia americana var. mexicana inflorescences and quercetin in the formalin test and in an arthritic pain model in rats

Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of aqueous extracts i.p., but not the same dose of methanol or hexane extract, produced an antinociceptive response in rats similar to that of tramadol (17.8 mg/kg i.p.). A dose-response curve from aqueous extract allowed the determination of ED₅₀ = 364.97 mg/kg in comparison to ED₅₀ = 10.35 mg/kg for tramadol in this model. A previous HPLC-DAD analysis corroborated by an HPLC-MS technique in this study demonstrated the flavonoid composition in this Tilia aqueous extract revealing the presence of glycosides mainly derived from quercetin. Thus, Tilia aqueous extract and quercetin were tested at 30 and/or 100 mg/kg dosages i.p. in the PIFIR and formalin models producing a significant and dose-dependent antinociceptive response resembling that produced by a total and a partial agonist of 5-HT_1A receptors like 8-OH-DPAT (0.1 mg/kg, s.c.) and buspirone (5 mg/kg, i.p.), respectively. In all the treatments, antinociceptive response was inhibited in the presence of WAY 100635 (0.12 mg/kg, i.p.). Our results support the analgesic activity of T. americana var. mexicana inflorescences attributed by folk medicine; they also indicate that quercetin is partly responsible for this pharmacological activity that is likely mediated by serotonin 5-HT_1A receptors.     

Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds

Context: Lippia species (Verbenaceae) are widely used in Latin America and Africa as folk medicine for their tranquilizing properties.

Objective: To evaluate the anxiolytic-like effects and safety of Lippia graveolens Kunth. by exploring its aqueous and organic leaf extracts and identifying the responsible chemical constituents.

Material and methods: Aqueous and organic extracts (hexane, ethyl acetate and methanol) were pharmacologically evaluated at several doses. Chemical constituents were identified using MS, NMR and GC-MS analysis. The isolated compounds (3?mg/kg, i.p.), extracts (1, 3, 10 and 30?mg/kg, i.p.), and the reference drug diazepam (0.1?mg/kg, i.p.) were assessed in CD-1 mice using experimental behavioural models: open-field, cylinder, hole-board, plus-maze and sodium pentobarbital-induced hypnosis, as well as their acute toxicity (LD₅₀).

Results: After administration of the extracts and bioactive compounds, a significant anxiolytic-like response from 1?mg/kg, i.p. was observed, resembling the effect of diazepam. Major presence of thymol (33.40%) was observed in the hexane extract; whereas for the first time in this species a p-cymene?+?thymol mixture (9.78%), naringenin (0.18%) and cirsimaritin (1.16%) were obtained as bioactive constituents of the ethyl acetate crude extract. Acute toxicity was calculated to be LD₅₀ =?1000?mg/kg for the crude hexane extract, lower in comparison to the other extracts analyzed (LD₅₀ >?2000?mg/kg).

Discussion and conclusion: Our results suggest that L. graveolens exerts anxiolytic-like activity involving many kinds of constituents, mainly of the terpenoid and flavonoid nature. These results reinforce the potential use of this species in the therapy of anxiety.     

Postcoital contraceptive efficacy and hormonal profile of Lepidium capitatum

Hexane soluble fraction of the Lepidium captiatum plant collected in Himachal Pradesh, India, was administered orally to colony bred albino mice, rats, and golden hamsters to test the plant's postcoital antifertility efficacy and estrogenic and antiestrogenic activities. 2.5 kg of the whole air-dried and powdered plant was extracted 4 times with 90% ethanol, which was evaporated under reduced pressure. The resultant aqueous suspension was partitioned 3 times with hexane and concentrated under vacuum to achieve the hexane soluble and hexane insoluble fractions. Oral administration of 250 mg/kg of crude ethanolic extract of the whole plant on postcoital days 1-5 prevented pregnancy in about 77% of mated female rats. The hexane soluble fraction inhibited pregnancy in 100% of the rats at a dose of 250 mg/kg and in 50% at 125 mg/kg. In comparison to controls, there was a significant reduction in implantation number at both 125 mg/kg and 625 mg/kg doses. The extract failed to prevent pregnancy in hamsters even at a daily dose of 500 mg/kg on postcoital days 1-5. No contraceptive efficacy of the hexane insoluble extract was observed in rats or hamsters. The extract exhibited potent estrogenic activity at the contraceptive dose, without antiestrogenic activity. A significant uterotrophic effect was seen even at 1/40 of the contraceptive dose. When administered orally for 3 consecutive days, the hexane soluble fraction induced normal implantations at 250 mg/kg and lower doses in adult female mice undergoing experimentally induced delayed implantation. The maximum response in terms of the percentage of pregnant animals and the average number of implantations was observed at 125 mg/kg dose. The experimental results confirm the frank estrogenicity of the extract.     

Antinociceptive Properties of the Hydroalcoholic Extract,Fractions and Compounds Obtained from the Aerial Parts of Baccharis illinita DC in Mice

Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30–1000 mg/kg orally) produced a dose‐related inhibition of the acetic acid‐induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, α‐spinasterol and oleanolic acid (0.00001–10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid‐induced pain. The hexane fraction (300–1000 mg/kg orally) produced inhibition of both phases of formalin‐induced pain. Moreover, the hexane fraction (30–600 mg/kg orally) also caused a dose‐dependent inhibition of glutamate‐induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N‐methyl‐d ‐aspartic acid, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid, tumour necrosis factor‐α and interleukin‐1β. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non‐selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro‐inflammatory cytokines. Finally, baurenol, α‐spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.     

Antiulcerogenic activity of fractions and 3,15-Dioxo-21α-hydroxy friedelane isolated from Maytenus robusta (Celastraceae)

The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21α-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21α-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.     

Evaluation of the analgesic and anti-inflammatory activities of <Emphasis Type="Italic">Curcuma mangga</Emphasis> Val and Zijp rhizomes

The effects of Curcuma mangga ethanolic extract (CME) and its fractions, e.g., aqueous, chloroform, ethyl acetate, and hexane fractions, from C. mangga rhizome were investigated on nociceptive responses using writhing, hot plate, and formalin tests in mice and inflammatory models using carrageenan-induced rat paw edema and croton oil-induced mouse ear edema. The results showed that CME and all fractions (200 mg/kg, p.o.) significantly reduced the number of writhings. Oral administration (p.o.) of CME, chloroform, and hexane fractions (200 mg/kg) significantly prolonged the latency time, whereas aqueous and ethyl acetate fractions were inactive. The activities of CME, chloroform, and hexane fractions were abolished by naloxone (2 mg/kg, intraperitoneal (i.p.)). CME and all fractions at the dose of 200 mg/kg significantly produced antinociception in both early and late phases of the formalin test. CME, chloroform, and hexane fractions were more prominent in licking inhibition than those of the aqueous and ethyl acetate fractions. CME and all fractions (150 mg/kg, p.o.) showed significant reduction of rat paw edema. The order of activity on inhibition of paw edema at 4 h was chloroform fraction > hexane fraction > ethyl acetate fraction > CME > aqueous fraction. When topically applied at 0.5 mg/ear, CME and all fractions suppressed ear edema induced by croton oil. CME and chloroform fraction showed a greater inhibition by 53.97 and 50.29%, respectively. These results suggested that CME and its fractions, especially chloroform and hexane fractions from C. mangga rhizome, possessed centrally acting analgesic as well as anti-inflammatory activities.     

Antinociceptive and anti-inflammatory effects of isolated fractions from Apium graveolens seeds in mice

The antinociceptive and anti-inflammatory effects of the aqueous and hexane extracts obtained from Apium graveolens L. (Apiaceae) seeds were evaluated. Formalin and xylene-induced ear edema tests were used in mice. The fractions were administered intraperitoneally at doses of 100-500?mg/kg body weight (BW). Both extracts with the xylene-induced ear edema test showed significant anti-inflammatory activity at all doses as compared with control. Only the hexane fraction reduced the nociception produced by formalin solution in the first phase (0-5?min) at 300, 400, and 500?mg/kg BW, and in the second phase (20-30?min) at 500?mg/kg BW. It is concluded that the hexane fraction has major contribution to the overall antinociceptive activity. Both fractions showed remarkable anti-inflammatory effect which supported the traditional use of Apium graveolens in diseases associated with inflammation.     

Limited anxiolytic-like effects of non-benzodiazepine hypnotics in rodents

The present experiments compared the anxiolytic-like effects of the benzodiazepine (BZD) hypnotic triazolam with those of four non-BZD hypnotics including one non-selective (zopiclone) and three omega1-BZD selective (zolpidem, zaleplon and SX-3228) receptor ligands, in classical animal models including conflict tests (punished lever pressing and punished drinking tests in rats) and exploratory models (elevated plus-maze test in rats and light/dark choice test in mice), and a recently developed mouse defence test battery (MDTB) which has been validated for the screening of anxiolytic drugs. Results from both conflict procedures showed that zopiclone (0.3-10 mg/kg) produced anxiolytic-like effects comparable to those of triazolam (0.1-3 mg/kg), whereas the selective omega1-BZD receptor hypnotics zolpidem (0.3-3 mg/kg), zaleplon (0.1-3 mg/kg) and SX-3228 (0.1-1 mg/kg) displayed weaker and/or non-specific anxiolytic-like effects. Similarly, in the light/dark test in mice, zolpidem (0.1-1 mg/kg), zaleplon (0.3-10 mg/kg) and SX-3228 (0.03-0.3 mg/kg) showed a reduced potential to produce anxiolytic-like effects as compared to the non-selective omega-BZD receptor hypnotics triazolam (0.03-1 mg/kg) and zopiclone (1-30 mg/kg). In the elevated plus-maze test, zopiclone (1-10 mg/kg), zolpidem (0.1-1 mg/kg), zaleplon (0.3-3 mg/kg) and SX-3228 (0.1-1 mg/kg) displayed anxiolytic-like activity at doses close to those producing behavioural impairment, whereas triazolam (0.03-1 mg/kg) exhibited anxiolytic-like effects over a wide dose range in the absence of decreases in general activity. In the MDTB, zaleplon (0.3-10 mg/kg) decreased all defensive responses, a profile which was similar to that of triazolam (0.03-1 mg/kg), while zopiclone (1-30 mg/kg), zolpidem (0.3-10 mg/kg) and SX-3228 (0.03-1 mg/kg) had fewer effects on defensive behaviours with several effects occurring only at motor-impairing doses. Taken together, these results demonstrate that, although selective omega1-BZD receptor hypnotics display anxiolytic-like activity, the effects are generally weaker than those observed with non-selective omega-BZD receptor selective hypnotics such as triazolam or zopiclone. In particular, the anxiety-reducing potential of the omega1-BZD receptor selective compounds is limited to certain anxiety measures and may be confounded and/or masked by behavioural suppression.     

Assessment of anti-inflammatory,antinociceptive, immunomodulatory,and antioxidant activities of Cajanus cajan L. seeds cultivated in Egypt and its phytochemical composition

Context: Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine.

Objectives: The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied.

Materials and methods: Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400?mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated.

Results and conclusion: Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, β-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-β-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-β-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400?mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400?mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC₅₀) value: 9.07 μg/ml).     

Chronic treatment with desipramine induces an estrous cycle-dependent anxiolytic-like action in the burying behavior, but not in the elevated plus-maze test.

The effect of chronic desipramine (DMI, 2.5 mg/kg x 21-26 days) treatment in female rats in two anxiety paradigms was assessed: the burying behavior (BB) and the elevated plus-maze (EPM) tests. In the BB test DMI produced a significant decrease in burying in ovariectomized rats, an effect considered as anxiolytic-like. In cycling females, DMI also reduced the cumulative BB most notably in proestrus rats. However, in diestrus rats no anxiolytic-like actions were observed. In addition, DMI increased BB latencies in proestrus and estrus rats. In the EPM test, DMI produced anxiolytic-like actions only in ovariectomized rats, while no significant actions were found in cycling females. Finally, the chronic treatment with DMI produced a general reduction in the ambulatory behavior of rats in all estrous cycle phases. Results are discussed on the basis of the differences between both anxiety paradigms and the probable relationship between the steroids secreted during proestrus and chronic DMI treatment.     

Anxiolytic-like effects of preferential dopamine D3 receptor agonists in an animal model

The aim of the present study was to examine a potential anxiolytic-like action of (+)-7-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (7-OH-DPAT), a preferential dopamine D(3) receptor agonist, and (N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-2-naphthylcarboxamide (BP 897), partial dopamine D(3) receptor agonist. Diazepam was used as a reference compound. The anxiolytic-like effect of those drugs was tested in the conflict drinking test (Vogel test) in male Wistar rats. The obtained results showed that 7-OH-DPAT and BP 897 (like diazepam) induced anxiolytic-like effects in the conflict drinking test. 7-OH-DPAT (0.05 and 0.1 mg/kg), BP 897 (0.5 mg/kg) and diazepam (5 and 10 mg/kg), tested at the effective doses in an animal model, did not affect motor coordination but produced significant reduction in exploratory activity in the open field test. These data suggest that preferential dopamine D(3) agonists may play a role in the therapy of anxiety, however, further studies are necessary to elucidate the mechanism of these actions.     

Orchidectomy sensitizes male rats to the action of diazepam on burying behavior latency: role of testosterone

The anxiolytic-like effect of diazepam (0.0, 0.5, 1.0 mg/kg) on the cumulative burying behavior and the burying behavior latency were compared between intact and castrated male rats. In both groups a clear reduction in cumulative burying, denoting an anxiolytic-like response, was observed. However, castrated males were more sensitive to diazepam in the burying behavior latency, a parameter indicating reactivity. Thus, orchidectomized males showed an increase in burying behavior latency after 1.0 mg/kg diazepam treatment. This dose has no effect on burying behavior latency in intact animals. The higher sensitivity to diazepam on reactivity seems to be androgen dependent because it was reversed by chronic treatment with testosterone propionate (TP, 0.0625 mg/rat for 2 weeks). TP (0.0, 0.0625, 0.125, 0.25, 0.5 and 1.0 mg/rat) produced a dose-dependent reduction in burying behavior after chronic treatment (four injections separated 48 h). At no dose did TP affect burying behavior latency. These results indicate that some actions of diazepam vary in males depending upon the endocrine milieu. Results also support the idea of androgens possessing anxiolytic-like actions.     

Involvement of the opioid system in the anxiolytic-like effects induced by Delta(9)-tetrahydrocannabinol

RATIONALE: Recent studies have shown that several pharmacological actions induced by cannabinoids, including antinociception and reward, involve the participation of the endogenous opioid system. OBJECTIVES: The present study was designed to examine the possible involvement of the different opioid receptors in the anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC). METHODS: The administration of a low dose of THC (0.3 mg/kg) produced clear anxiolytic-like responses in the light-dark box, as previously reported. The effects of the pretreatment with the CB(1) cannabinoid receptor antagonist, SR 141716A (0.5 mg/kg), or the micro -opioid receptor antagonist, beta-funaltrexamine (5 mg/kg), the delta-opioid receptor antagonist, naltrindole (2.5 mg/kg) and the kappa-opioid receptor antagonist, nor-binaltorphimine (2.5 mg/kg) were evaluated on anxiolytic-like responses induced by THC. RESULTS: SR 141716A completely blocked the anxiolytic-like response induced by THC, suggesting that this effect is mediated by CB(1) cannabinoid receptors. The micro -opioid receptor antagonist beta-funaltrexamine and the delta-opioid receptor antagonist naltrindole, but not the kappa-opioid receptor antagonist nor-binaltorphimine, abolished THC anxiolytic-like effects, suggesting an involvement of micro - and delta-opioid receptors in this behavioural response. CONCLUSIONS: These results demonstrate that the endogenous opioid system is involved in the regulation of anxiety-like behaviour by cannabinoids and provide new findings to clarify further the interaction between these two neuronal systems.     

The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists.

Neurokinin NK1 receptor antagonists may have therapeutic potential in the treatment of anxiety and depression. Species variants in the NK1 receptor result in reduced affinity of NK1 receptor antagonists at rat and mouse NK1 receptors, making it difficult to test NK1 antagonists in traditional preclinical models of anxiety and depression. Gerbil NK1 receptors are similar in homology to the human NK1 receptor. In a companion article, we described the anxiety-like behavioral profile of gerbils on an adapted elevated plus-maze, and the ability of anxiolytic drugs to produce anti-anxiety effects in the gerbil elevated plus-maze. The aim of the present study was to determine whether oral (p.o.) administration of the NK1 receptor antagonists MK-869, L-742,694, L-733,060, CP-99,994, and CP-122,721 produced anxiolytic-like effects in the gerbil elevated plus-maze. Upon testing, all five NK1 antagonists produced anxiolytic-like effects. MK-869 (0.01-3 mg/kg) was the most potent NK1 antagonist, producing anxiolytic-like effects on percentage of open arm time, percentage of open arm entries, stretch-attend postures, and head dips at 0.03-0.3 mg/kg doses. L-742,694 (1-30 mg/kg) and L-733,060 (1-10 mg/kg) produced anxiolytic-like effects on percentage of open arm time and stretch-attend postures at 3-10 mg/kg doses. CP-99,994 (3-30 mg/kg) only produced an anxiolytic-like effect on stretch-attend postures. CP-122,721 (3-30 mg/kg) produced an anxiolytic-like effect on percentage of open arm time at 30 mg/kg. The order of potency of the NK1 antagonists to increase percentage of open arm time was very similar to their potency to block NK1 agonist-induced foot-tapping. These studies demonstrate that neurokinin NK1 receptor antagonists produce anxiolytic-like effects in a novel gerbil elevated plus-maze, and suggest that this is an appropriate model to test NK1 antagonists for preclinical anxiolytic activity.     

Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression

The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.     

The gerbil elevated plus-maze I: behavioral characterization and pharmacological validation.

Several neurokinin NK1 receptor antagonists currently being developed for anxiety and depression have reduced affinity for the rat and mouse NK1 receptor compared with human. Consequently, it has proven difficult to test these agents in traditional rat and mouse models of anxiety and depression. This issue has been overcome, in part, by using non-traditional lab species such as the guinea pig and gerbil, which have NK1 receptors closer in homology to human NK1 receptors. However, there are very few reports describing the behavior of gerbils in traditional models of anxiety. The aim of the present study was to determine if the elevated plus-maze, a commonly used anxiety model, could be adapted for the gerbil. Using a specially-designed elevated plus-maze, gerbils exhibited an 'anxious' behavioral profile similar to that observed in rats and mice, i.e., reduced entries into, and time spent exploring, an open, aversive arm. The anxiolytic drugs diazepam (0.03-3 mg/kg i.p.), chlordiazepoxide (0.3-10 mg/kg i.p.), and buspirone (0.3-30 mg/kg s.c.) increased open arm exploration and produced anxiolytic-like effects on risk-assessment behaviors (reduced stretch-attend postures and increased head dips). Of particular interest, the antidepressant drugs imipramine (1-30 mg/kg p.o.), fluoxetine (1-30 mg/kg, p.o.) and paroxetine (0.3-10 mg/kg p.o.) each produced some acute anxiolytic-like activity, without affecting locomotor activity. The antipsychotic, haloperidol, and the psychostimulant, amphetamine, did not produce any anxiolytic-like effects (1-10 mg/kg s.c). The anxiogenic beta-carboline, FG-7142, reduced time spent in the open arm and head dips, and increased stretch-attend postures (1-30 mg/kg, i.p.). These studies have demonstrated that gerbils exhibit an anxiety-like profile on an elevated plus-maze, and that the gerbil elevated plus-maze may have predictive validity for anxiolytics, and antidepressants with potential anxiolytic-like effects.     

Effects of Hypericum perforatum and paroxetine in the mouse defense test battery

Since (a) Hypericum perforatum shows anxiolytic-like effect in some animal models, (b) antidepressant drugs (AD) have been used as the main drug treatment for panic disorder (PD), (c) AD are also effective in generalized anxiety disorder (GAD), and (d) H. perforatum exhibits antidepressant activity, it was hypothesized that H. perforatum might possess an antipanic-like and/or anxiolytic-like effect. Previous studies with the mouse defense test battery (MDTB) have suggested that this model may be useful for the investigation of anxiolytic-like and antipanic-like compounds. Thus, the aim of the present study was to evaluate the effect of H. perforatum extract in the MDTB. The effect of acute, subchronic (7 days), and chronic (21 days) H. perforatum (150 and 300 mg/kg) extract administration was evaluated in mice submitted to the MDTB. Paroxetine (5 mg/kg), a selective serotonin re-uptake inhibitor with anxiolytic and antipanic effect, was used as a positive control. The results showed that 21 days of repeated administration of H. perforatum 300 mg/kg and paroxetine 5 mg/kg reduced flight reactions (number of avoidances, avoidance distance, and overall flight speed) to the presence of the predator. While the effect of paroxetine confirms that MDTB is useful for the detection of antipanic-like drugs, the effect of H. perforatum suggests a putative antipanic-like effect for this extract. Moreover, after 21 days of repeated administration, paroxetine increased the number of approaches/withdrawals and reduced the number of upright postures, suggesting a partial anxiolytic-like effect, while H. perforatum only reduced the number of upright postures. The present results suggest anxiolytic-like and antipanic-like effects of H. perforatum extract. However, it should be emphasized that the risk assessment (the main index of anxiety) was not affected by the extract, while the attack reactions were only weakly modified.     

Evaluation of the neuropharmacological effects of Gardenin A in mice

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1–25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light–dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABA_A receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1–10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.     

Adenosine, the anxiolytic-like principle of the Arillus of Euphoria longana

According to traditional usage, the extract of Longan Arillus was tested for its anxiolytic-like effect by application of the Vogel-type anti-conflict method in mice. The extract indicated significant activity at a dose of 2 g/kg, s.c., and results of the bioassay-oriented isolation revealed adenosine to be the active principle. Adenosine produced the anti-conflict effect significantly at a dose of 30 mg/kg, s.c. Adenine, uridine, and 5-methyluridine did not exhibit the effect, although these compounds were isolated from the extract. Some other related compounds such as AMP and c-AMP showed no effect, except for inosine. Adenosine also contributed to the analgesic effect which was observed in the extract by the writhing method.     

Anti-inflammatory and analgesic activities of the latex containing triterpenes from Himatanthus sucuuba

Some triterpenes and iridoids were previously isolated from the stem bark of Himatanthus sucuuba. The latex from Himatanthus sucuuba is used in popular amazonian medicine as an anti-inflammatory remedy. Fractions of the latex were pharmacologically evaluated with a view to verify this popular use in the carrageenan-induced rat paw edema and in the acetic acid-induced mouse constriction tests. The hexane fraction inhibited the edema formation by 35.9% at a dose of 200 mg/kg (p.o.) but no activity was observed at 100 mg/kg (p.o.). The triterpenes present in the hexane fraction were identified as lupeol acetate, alpha-amyrin and lupeol cinnamates. The fraction containing only cinnamates inhibited the edema and the abdominal constrictions by 50-40% and 57.9%, respectively, at 100 mg/kg (p.o.). Among all the fractions studied, the fraction containing only cinnamates showed the greatest anti-inflammatory activity which suggests that these compounds were responsible for the previously described activity of the crude extract.