RESUMO
Ziziphus joazeiro Mart. is an endemic plant of the Caatinga that presents a great socioeconomic importance for the Northeast and Semiarid Region of Brazil. In view of this, this study aimed to evaluate the antibacterial activity and anxiolytic-like effects of Ziziphus joazeiro Mart leaves in adult zebrafish (Danio rerio). The characterization of the main classes of metabolites was performed through chemical reactions. The antibacterial and antibiotic potentiating activity was evaluated by broth microdilution assays. The 96 h acute toxicity, open field test and anxiety models test was evaluated in vivo on adult zebrafish. The results obtained in the phytochemical prospection evidenced the presence of flobabenic tannins, leucoanthocyanidins, flavonois, flavonones, catechins, alkaloids, steroids, and triterpenoids. EEFZJ did not show antibacterial activity for all microorganism tested (MIC ≥ 1024 µg/mL), but reduced the concentration required for bacterial growth inhibition in combination with gentamicin and norfloxacin against multidrug-resistant strains of S. aureus (SA10) and E. coli (EC06), exhibiting synergistic effect with these antibiotics (p<0.0001). In the tests in vivo, EEFZJ was found to be nontoxic, performing reduced locomotor activity and demonstrated an anxiolytic-like effect in adult zebrafish via GABAergic and Serotoninergic systems (5-HT1, 5-HT2A/2C and 5-HT3A/3B).
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Studies have shown that psychotropic drugs change rat behavior in the elevated plus-maze test (EPM). This study investigated whether static magnetic fields could alter alprazolam-induced rat behavior in the EPM. 66 male Wistar rats (270-300 g weight) were assigned to one of the following groups: Sham Magnetic + Saline (SMS), North Pole + Saline (NPS), South Pole + Saline (SPS), Sham magnetic + alprazolam (SMA), NP + alprazolam (NPA), and SP + alprazolam (SPA). After five days of static magnetic stimulation (3200 Gauss), they received alprazolam or saline (1 mg/kg), and their behavior was evaluated. Two-way ANOVA and Holm-Sidak post-hock were used, with a significant P value of <0.05. The SMA and NPA groups showed an increased number of entries and time in the open arms compared with the SMS group. SPA showed a decrease in these measures when compared to SMA [F(2,61) = 6.43 and F(2,61) = 3.72, respectively]. The SMA and NPA groups showed increased head dipping and end-arm activity compared with the SMS group. SPA showed a decrease in these measures when compared to SMA [F(2,61) = 3.37 and [F(2,61) = 4.72, respectively]. These results show that the south magnetic pole of a static magnetic field blocked the alprazolam effect in the space-time variables of the open arms and ethological anxiolytic-like behavior in the EPM.
Assuntos
Alprazolam , Ansiolíticos , Animais , Masculino , Ratos , Alprazolam/farmacologia , Ansiolíticos/farmacologia , Ansiedade , Comportamento Animal , Teste de Labirinto em Cruz Elevado , Campos Magnéticos , Aprendizagem em Labirinto , Ratos WistarRESUMO
Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography-mass spectrometry (GC-MS). This study evaluated the effects of CAE (10-100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED50 = 57 mg/kg). CAE (10-100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.
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BACKGROUND: There are over 500 species in the Passiflora genus, and while some of them are very well known in folk medicine for their anxiolytic effects, very little is known for the other genus representants, which could also present medicinal effects. OBJECTIVE: In this study, we performed an interspecific pharmacological comparison of five investigated Passiflora species, all native to Brazil, namely P. bahiensis, P. coccinea, P. quadrangularis, P. sidaefolia, and P. vitifolia. METHODS: Extracts were administered to mice before behavioral testing, including a general pharmacological screening and anxiolytic-like effect investigation. RESULTS: Three of the species (P. coccinea, P. quadrangularis, and P. sidaefolia) induced a decrease in locomotor activity of mice; P. coccinea also reduced the latency to sleep. Importantly, none of the species interfered with motor coordination. Oral administration evoked no severe signs of toxicity, even at higher doses. Regarding the anxiolytic-like profile, P. sidaefolia reduced the anxious-like behavior in the Holeboard test in a similar way to the positive control, Passiflora incarnata, while not affecting total motricity. CONCLUSION: These results indicated that P. coccinea, P. quadrangularis, and P. sidaefolia reduced the general activity of mice and conferred a calmative/sedative potential to these three species, which must be further elucidated by future investigations.
Assuntos
Ansiolíticos , Passiflora , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The aim of this study was to evaluate the anxiolytic-like effect of chrysophanol (CHRY), isolated from hexane extract of Senna cana stem and its possible mechanism of action. CHRY was obtained through chromatographic treatments and its identity was confirmed by uni and bidimensional RMN1H and RMN13C. Adult zebrafish (n = 6/group) were treated (with CHRY (4.0 or 12.0 or 40.0 mg/Kg; 20 µL; intraperitoneally) and submitted to acute toxicity and open field tests. Subsequently, other groups (n = 6/each) received CHRY for the analysis of its effect on the Light & Dark Test. The participation of the GABAergic system was also assessed using the diazepam (GABAA receptor agonist) and flumazenil (GABAA receptor antagonist). CHRY was considered non-toxic, it did not reduce the locomotor activity, and showed an anxiolytic-like effect. This effect was reduced by pre-treatment with flumazenil. The results suggest that CHRY is an anxiolytic-like agent mediated via the GABAergic system.
Assuntos
Ansiolíticos , Senna , Animais , Antraquinonas , Ansiolíticos/farmacologia , Ansiedade , Flumazenil/farmacologia , Receptores de GABA-A , Peixe-ZebraRESUMO
BACKGROUND: Plant lectins have shown promising neuropharmacological activities in animal models. OBJECTIVE: This study evaluated the effect of Dioclea altissima seed lectin (DAL) on adult zebrafish behavior. METHOD: Zebrafish (n=6/group) were treated (i.p.; 20 µL) with DAL (0.025; 0.05 or 0.1 mg/mL), vehicle or diazepam (DZP) and submitted to several tests (open field, light/dark preference or novel tank). Flumazenil, pizotifen or granisetron were administered 15 min before DAL (0.05 mg/mL), and the animals were evaluated on light/dark preference test. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: DAL decreased the locomotor activity of adult zebrafish (0.025; 0.05 or 0.1 mg/mL), increased the time spent in the upper region of the aquarium (0.025 mg/mL), and decreased the latency time of adult zebrafish to enter the upper region on the novel tank test. DAL (0.05 mg/mL) also increased their permanence in the light zone of the light/dark preference test. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and was prevented by pizotifen, granizetron and flumazenil. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors.
Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dioclea/metabolismo , Lectinas/metabolismo , Peixe-Zebra/metabolismo , Animais , Ansiolíticos/uso terapêutico , Modelos Animais de Doenças , Locomoção/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Receptores de GABA-A/metabolismo , SementesRESUMO
Chamomile is one of the most ancient medicinal herbs known to mankind and among its traditional uses are the calming effects. However, few studies explored its effects on the central nervous system (CNS). In this study we further proceed with structural elucidation of polysaccharides from chamomile tea. A highly substituted 4-O-methyl-glucuronoxylan (fraction SN-50R) was purified and chemically characterized, presenting Xyl:GlcA ratio of 1.7:1, Mw of 500 kDa and total sugar content of 98%. Its bioactivity on pain and on CNS was explored. Animals treated with SN-50R presented antinociceptive effect and a dose-dependent decrease in the number of crossings in the activity chamber and in the open field test, as well as a significant reduction in the number of marbles buried when compared to control. These results suggest that SN-50R presented sedative and anxiolytic-like effects and may be contributing for the calming effects obtained by chamomile tea ingestion.
Assuntos
Analgésicos/farmacologia , Ansiolíticos/farmacologia , Camomila/química , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Chá/química , Xilanos/farmacologia , Animais , Feminino , Masculino , Camundongos , Plantas Medicinais/química , Polissacarídeos/farmacologiaRESUMO
Piperazine derivatives are an attractive class of chemical compounds for the treatment of various mental illness. Herein, we demonstrated the synthesis of LQFM212, a piperazine derivative, behavioral evaluation in mice and computational studies. In neuropharmacological assessment, LQFM212 treatment at doses of 18, 54 or 162 µmol/kg increased the sleep duration in sodium pentobarbital-induced sleep test. LQFM212 at dose of 162 µmol/kg increased climbing time in the chimney test and decreased the number of squares crossed in the open field test, suggesting that LQFM212 in high doses reduces spontaneous movement. However, LQFM212 treatment at the doses of 18 or 54 µmol/kg increased the preference for the center of field which could be indicative of anxiolytic-like effects. In elevated plus maze and light-dark box tests, LQFM212 treatment altered all parameters observed that demonstrate anxiolytic-like activity. These effects were reversed by flumazenil, mecamylamine, WAY-100635 and PCPA, but not with ketanserin, showing that anxiolytic-like activity involve benzodiazepine site of GABAA receptor, nicotinic and serotonergic pathways. Molecular docking of LQFM212 showed that the ligand has more interactions with GABAA receptor than with 5-HT1A receptor. Despite the involvement of benzodiazepine site on anxiolytic-like effect of LQFM212, treatment with this compound did not alter cognitive function in the step-down avoidance test. In this sense, this piperazine derivative is a good prototype for treating anxiety disorders with putative mechanism of action.
Assuntos
Ansiolíticos/farmacologia , Simulação de Acoplamento Molecular , Piperazina/análogos & derivados , Piperazina/farmacologia , Piperazinas/farmacologia , Animais , Ansiedade/prevenção & controle , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Piperazinas/químicaRESUMO
Omega-3-enriched fish oil (FO) and caloric restriction (CR) are nutritional therapeutic approaches that exert an important impact on brain function, behavior, memory, and neuroprotection. Here, we investigate the synergic effects of both therapeutic approaches combined (CR + FO) on behavior (memory, anxiety-like behavior, antidepressant-like behavior), as well as its association with hippocampal brain-derived neurotrophic factor (BDNF) concentrations. Adult male Wistar rats were divided into four dietary groups: Control group (C) - chow ad libitum; CR group - 30 % CR, considering C group food intake; FO group - FO-enriched chow ad libitum; and CR + FO group - FO-enriched 30 % CR chow. After 12 weeks of dietary treatment, behavioural analysis set was conducted, and hippocampal BDNF concentrations were measured. FO group presented anxiolytic-like and antidepressant-like behaviors as well as improved memory in the Morris' water maze. These effects were attenuated by the combined CR + FO treatment. FO group also presented higher BDNF concentrations. There was a positive association between the number of entries in the platform quadrant in the MWM and hippocampal BDNF concentrations (ß = 0.39; R² = 0.15; p = 0.042) and an inverse association between forced swim immobility time and BDNF concentrations (ß = -0.39; R² = 0.15; p = 0.041). Taken together, our data showed that the 12-week FO dietary treatment promoted anxiolytic-like and antidepressant-like behaviors as well as memory improvement, and these effects were associated with BDNF concentrations. Synergic effects of interventions attenuated FO-related behavioral responses and BDNF concentrations and probably reduced hippocampal neuroplasticity.
Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Restrição Calórica , Depressão/tratamento farmacológico , Óleos de Peixe/farmacologia , Hipocampo/efeitos dos fármacos , Animais , Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Óleos de Peixe/uso terapêutico , Hipocampo/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: Plant lectins have shown promising biological activities in the central nervous system (CNS). OBJECTIVE: This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. METHODS: Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.
Assuntos
Ansiolíticos , Dioclea , Animais , Ansiolíticos/farmacologia , Antidepressivos , Comportamento Animal , Lectinas , Camundongos , Extratos Vegetais , SementesRESUMO
The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4'-[(2E) -3- (3-nitrophenyl) -1- (phenyl) prop-2-en-1-one] acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies.
Assuntos
Acetamidas/farmacologia , Ansiolíticos/farmacologia , Chalcona/farmacologia , Serotonina/metabolismo , Acetamidas/química , Animais , Ansiolíticos/química , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Chalcona/análogos & derivados , Descoberta de Drogas , Locomoção/efeitos dos fármacos , Simulação de Acoplamento Molecular , Receptores 5-HT1 de Serotonina/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismoRESUMO
The aim was to evaluate the diuretic and neuropharmacological actions of d-pinitol and describe a possible mechanism of action. The diuretic effects of d-pinitol were evaluated using mice placed in metabolic cages. The sedative, anxiolytic-like, antidepressant-like, and anticonvulsant effects of 1-100 mg/kg d-pinitol were assessed. The possible mechanisms of action of the anxiolytic-like, antidepressant-like, and anticonvulsant effects of d-pinitol were evaluated using inhibitors. d-pinitol lacked diuretic effects. However, d-pinitol showed the highest anxiolytic-like actions (ED50 = 70 mg/kg p.o. in mice) in the cylinder exploratory test and the highest antidepressant-like activity in the forced swimming test (ED50 = 26 mg/kg p.o. in mice). d-pinitol (100 mg/kg) exerted anticonvulsant actions in the pentylenetetrazole-induced seizures test. The pre-treatment with 2 mg/kg flumazenil reverted the anxiolytic-like actions and the anticonvulsant effects of d-pinitol, whereas the pre-treatment with 1 mg/kg yohimbine and 0.05 mg/kg prazosin abolished the antidepressant effects of d-pinitol. PRACTICAL APPLICATIONS: d-pinitol (3-O-methyl-d-chiro-inositol) is a polyol found in many fruits, as well as in many members of the Leguminosae and Fabaceae families. The results propose that this compound could contribute in the treatment of anxiety, depression, and convulsions. The findings suggest the possible participation of the GABAergic system in the anxiolytic-like and anticonvulsant actions of d-pinitol, whereas the noradrenergic system is probably involved in the antidepressant effects of d-pinitol. This study provides new information about other pharmacological uses for d-pinitol.
Assuntos
Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Flumazenil/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Inositol/análogos & derivados , Pentilenotetrazol/efeitos adversos , Convulsões/induzido quimicamente , Ioimbina/efeitos adversos , Animais , Inositol/análise , Camundongos , Camundongos Endogâmicos BALB C , NeurofarmacologiaRESUMO
The piperazine derivatives correspond to an extensive chemical class of compounds with numerous neuropharmacological activities, including antidepressant (e.g., nefazodone, trazodone) and anxiolytic (e.g., buspirone) properties. Therefore, aiming to identify a new antidepressant and antianxiety lead-compound, our group designed, synthesized, and investigated the effects of a new piperazine compound, namely, LQFM104, on the behavior of mice. Male albino Swiss mice were treated with LQFM104 prior to predictive behavioral tests as open field (OFT), elevated plus maze (EPM), forced swimming (FST), and tail suspension tests (TST). The participation of the serotonergic system was evaluated by pretreatment with a 5-HT1A antagonist receptor (WAY100635) and serotonin (5-HT) synthesis inhibitor (p-chlorphenylalanine, pCPA) before oral administration of LQFM104 and behavioral tests. The treatment with LQFM104 did not interfere with locomotor activity but revealed suggestive data of anxiolytic-like effects by the increase in the time spent in the center of the OFT. This activity was confirmed by the results obtained in the EPM, and it was abolished after pretreatment with WAY100635 and pCPA. The immobility time decreased in both the FST and TST. The antidepressant-like activity was completely abolished after WAY100635 pretreatment. Altogether, these data revealed that LQFM104 possesses anxiolytic and antidepressant-like properties in behavioral tests on mice, and these activities are possibly mediated, directly and/or indirectly, by serotonergic pathways.
Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Piperazinas/farmacologia , Receptor 5-HT1A de Serotonina/fisiologia , Serotonina/fisiologia , Animais , Ansiolíticos/química , Antidepressivos/química , Relação Dose-Resposta a Droga , Elevação dos Membros Posteriores/métodos , Elevação dos Membros Posteriores/psicologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Piperazina , Piperazinas/química , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/fisiologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologiaRESUMO
In the scope of a research program aimed at developing new drugs for the treatment of central nervous system diseases, we describe herein the synthesis and pharmacological evaluation of 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one (LQFM180). This compound showed antioxidant activity in two models, electroanalytical assays, and DPPH activity. Moreover, in behavioral tests as the open field test LQFM180 (9.4, 18.8, and 37.6 mg/kg, per oral (p.o.)), we detected anxiolytic-like activity. In the sodium pentobarbital-induced sleep test, LQFM180, in all doses, decreased the latency to sleep and increased sleep duration, indicating central depressant activity; moreover, in the chimney test, LQFM180 did not alter motor activity. LQFM180 (18.8 mg/kg, p.o.) increased the time and number of entries on open arms in the elevated plus maze test, suggesting anxiolytic-like activity, which was reversed by NAN-190 and p-chlorophenylalanine, indicating a role of the serotonergic pathway on this effect. In the forced swimming test, LFQM180 (18.8 mg/kg, p.o.) decreased immobility time, suggesting antidepressant-like activity, which was reversed by monoaminergic antagonists, indicating a role for the serotonergic, noradrenergic, and dopaminergic pathways. Competition binding assays showed that LQFM180 was able to bind to the α1B, 5-HT1A, and D2 receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.
Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Piperazinas/farmacologia , Animais , Ansiolíticos/química , Antidepressivos/química , Antioxidantes/química , Comportamento Animal/efeitos dos fármacos , Compostos de Bifenilo/química , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Picratos/química , Piperazinas/química , Ratos Wistar , Receptor 5-HT1A de Serotonina/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Receptores de Dopamina D2/metabolismoRESUMO
OBJECTIVE: Argemone mexicana is a Papaveracea plant; some reports have shown their antibacterial, anti-cancer, sedative and probably anti-anxiety properties. From their aerial parts, flavonoids and alkaloids have been isolated, which are intrinsically related to some actions on the central nervous system. The aim of this study was to evaluate the anxiolytic-like effects of the plant, using its ethanolic extract and alkaloid-enriched extract obtained from fresh leaves. MATERIAL AND METHODS: Phytochemical screening was carried out together with evaluation of antioxidant capacity and the enrichment of alkaloids present in the extract. Subsequently, 100 and 200 mg/kg doses of ethanolic extract and alkaloid-enriched extract (200 µg/kg) were intraperitoneally administered to female Wistar rats, which were exposed to elevated plus maze (EPM) test. Picrotoxin (1 mg/kg), a non-competitive gamma-aminobutyric acid A (GABAA) chloride channel antagonist, was used in experimental procedures to evaluate if this receptor is involved in the anxiolytic-like effects of A. mexicana. To discard motor effects associated with the treatments, the rats were evaluated by the locomotor activity test. RESULTS: Only the ethanolic extract at 200 mg/kg and alkaloid-enriched extract (200 µg/kg) produced anxiolytic-like effects similarly to diazepam 2 mg/kg on EPM test, without affecting locomotor activity. Meanwhile, the administration of picrotoxin blocked anti-anxiety effect of alkaloid-enriched extract of the plant. CONCLUSION: These results showed that A. mexicana is a potential anxiolytic agent and we suggest that this effect is mediated by the GABAA receptor. These effects are related to the presence of alkaloids.
RESUMO
Anxiety is a serious disorder with symptoms manifested at the psychological, behavioral, and physiological levels, accompanied by alterations in the serotonergic system and monoaminergic signaling. In this study, the anxiolytic-like effect of 2-phenylethynyl butyltellurium (PEBT), in three well-consolidated anxiety mouse models (light-dark test, novelty suppressed-feeding, elevated plus-maze), was investigated. The involvement of the serotonergic system, synaptosomal [(3)H] serotonin (5-HT) uptake and monoamine oxidase (MAO A and B) activities on cerebral cortices of mice, was examined. Mice received PEBT (1mg/kg, by intragastric route, i.g.) or canola oil (10 ml/kg, i.g.) 30 min before behavioral tests. The results showed that PEBT was effective in increasing the time spent by mice in the illuminated side on the light-dark box and in the open arms on the elevated plus-maze. PEBT decreased the latency to begin eating on the novelty suppressed-feeding test, indicating an anxiolytic-like effect of PEBT. Furthermore, PEBT reduced [(3)H] 5-HT uptake and selectively inhibited MAO-A activity in cerebral cortex, suggesting the involvement of the serotonergic system in the mechanism of action of this tellurium compound.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Serotonina/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Monoaminoxidase/metabolismoRESUMO
Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75 mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble-burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75 mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.