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1.
Pharmacol Rep ; 72(1): 24-35, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016837

RESUMO

BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.


Assuntos
Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Animais , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ketamina/farmacologia , Ketamina/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Testes de Toxicidade
2.
Pharmacol Biochem Behav ; 181: 1-8, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30946884

RESUMO

Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg orally (gavage) for 30 days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.


Assuntos
Ansiedade/induzido quimicamente , Memória/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Neurônios Serotoninérgicos/efeitos dos fármacos , Vareniclina/farmacologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Modelos Animais , Atividade Motora/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Agonistas Nicotínicos/administração & dosagem , Ratos , Ratos Wistar , Serotonina/metabolismo , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/métodos , Vareniclina/administração & dosagem , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Ácido gama-Aminobutírico/metabolismo
3.
Pharmacol Biochem Behav ; 181: p. 1-8, 2019.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15967

RESUMO

Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3?mg/kg orally (gavage) for 30?days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.

4.
Pharmacol Biochem Behav, v. 181, p. 1-8, jun. 2019
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2734

RESUMO

Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3?mg/kg orally (gavage) for 30?days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.

5.
Basic Clin Pharmacol Toxicol ; 122(3): 305-309, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28944993

RESUMO

Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4ß2 and α3ß4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.


Assuntos
Agonistas Nicotínicos/efeitos adversos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Vareniclina/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Coração/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Agonistas Nicotínicos/administração & dosagem , Especificidade de Órgãos , Ratos Wistar , Reprodutibilidade dos Testes , Testes de Toxicidade Subaguda , Vareniclina/administração & dosagem , Ganho de Peso/efeitos dos fármacos
6.
Braz. j. vet. res. anim. sci ; 50(1): 33-42, 2013.
Artigo em Inglês | LILACS | ID: lil-687659

RESUMO

Pyrethroid insecticides are extensively used for pest control around the house, flea prevention for pets, and plant sprays for the home and in agriculture. Deltamethrin (DTM) is a Type II pyrethroid insecticide used to control a variety of insects in agriculture and domestic environments. The present study investigated the possible anxiogenic effects of DTM (1, 3, and 10 mg/kg) in rats using behavioral and neurochemical methods. We assessed general locomotor activity and behavior in the elevated plus maze and open field test. Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) increased striatal serotonin neurotransmitter and its metabolite, and (vii) did not alter motor coordination on the rotarod, grooming duration in the open field test, rectal temperature, or hippocampal neurotransmitter levels. These data suggest that DTM at the present doses and under these experimental conditions presented a similar profile to that of anxiogenic drugs, unrelated with the increased serotonin neurotransmission.


Inseticidas piretróides são amplamente utilizados para controle de pragas, como na prevenção de pulgas em animais de estimação e sprays de plantas para a casa e na agricultura. Deltametrina (DTM) é um inseticida piretróide tipo II usado para controlar uma variedade de insetos na agricultura e ambientes domésticos. O presente estudo investigou os possíveis efeitos ansiogênicos de DTM (1, 3 e 10 mg/kg) em ratos, utilizando métodos comportamentais e neuroquímicos. Foi avaliada a atividade locomotora geral e comportamento no labirinto em cruz elevado e teste de campo aberto. Os níveis de neurotransmissores e metabólitos no estriado e hipocampo também foram mensurados. DTM (i) reduziu a locomoção e a frequência de levantar, (ii) aumentou da duração da imobilidade, (iii) reduziu o tempo de interacção social, (iv) reduziu a percentagem de entradas e tempo gasto nos braços abertos do elevado labirinto em cruz, (v) reduziu o número de cruzamentos no centro do labirinto em cruz elevado, (vi) aumentou neurotransmissor serotonina e de seu metabólito estriatal, e (vii) não alterou a coordenação motora no rotarod, duração do grooming no teste de campo aberto, temperatura retal, ou níveis de neurotransmissores do hipocampo. Estes dados sugerem que DTM nas presentes doses e sob estas condições experimentais apresentaram um perfil semelhante ao de drogas ansiogénicas, não relacionados ao aumento da serotonina estriatal.


Assuntos
Animais , Ansiedade , Inseticidas/análise , Comportamento Animal , Controle de Pragas/instrumentação , Ratos
7.
J. Health Sci. Inst ; 30(4)out.-dez. 2012. ilus
Artigo em Inglês | LILACS | ID: lil-673923

RESUMO

Objective - To assess, in this preclinical study, the effectiveness of a herbal medicine developed from a group of plants of the genus Ilexin the adjuvant treatment of obesity in rats fed with a high-fat diet. Phytotherapy is becoming increasingly popular both for the results it yields in several pathologies and because they are growing herbal medicine studies showing its effectiveness. Methods - Male and female rats were fed with a high-fat diet for one month. The diet was then replaced by a chow diet. All male and female rats received the PholiaNegra(X´Tract Vetorized)TM or water. The treatment was orally administered twice a day over 30 days. Body weight gain was assessed weekly and, at the end of treatment, the total body weight gain was calculated. A positive control with sibutramine (7.5 mg/kg, twice a day, orally, over 30 day was also included. Results - A significant reduction in weekly body weight gain, as well as in total weight gain, in both male and female rats after the herbal medicine administration. The index of body weight loss showed that PholiaNegra (X´TractVetorized)TM was more effective in reducing body weight in female than in male rats. The sibutramine treatment showed the same profile as PholiaNegra (X´Tract Vetorized)TM treatment. Conclusion - The present data indicate that PholiaNegra (X´Tract Vetorized)TM herbal medicine was effective in decreasing body weight in male and female rats submitted to a high-fat diet, and showed a similar profile to that of sibutramine.


Objetivo - Avaliar, neste estudo pré-clínico, a eficácia de um medicamento desenvolvido a partir de um grupo de plantas do gênero Ilex no tratamento adjuvante da obesidade em ratos alimentados com uma dieta hipercalórica. A fitoterapia está se tornando cada vez mais popular, tanto pelos resultados positivos em diversas doenças e porque estão crescendo estudos de medicina de ervas que mostram a sua eficácia. Métodos - Ratos machos e fêmeas foram alimentados com uma dieta rica em gordura durante um mês. A dieta foi então substituída por uma ração normal do biotério. Todos ratos e ratas foram tratado com PholiaNegra (X´Tract Vetorized)TM ou água. O tratamento foi administrado por via oral, duas vezes por dia durante 30 dias. O ganho de peso corporal foi avaliado semanalmente e, no final do tratamento, o ganho de peso total foi calculado. Como controle positivo empregou-se a sibutramina (7,5 mg/kg, duas vezes por dia, por via oral, durante 30 dias. Resultados - Observou-se redução significativa no ganho de peso corporal semanal, bem como do ganho de peso total, tanto nos ratos machos e fêmeas, após a administração do medicamento à base de plantas. O índice de perda de peso corporal mostrou que Pholia-Negra (X´Tract Vetorized)TM foi mais eficaz na redução do peso corporal nas fêmeas do que em ratos machos. O tratamento com sibutramina mostrou o mesmo perfil obtido com o tratamento com PholiaNegra (X´Tract Vetorized)TM. Conclusão - Os presentes dados indicam que PholiaNegra (X´Tract Vetorized)TM foi eficaz em diminuir o peso corporal em ratos machos e fêmeas submetidos a uma dieta rica em gordura,e mostrou um perfil semelhante ao da sibutramina.


Assuntos
Animais , Fitoterapia/estatística & dados numéricos , Fitoterapia/tendências , Obesidade/diagnóstico , Obesidade/prevenção & controle , Plantas Medicinais
8.
Braz. j. vet. res. anim. sci ; 49(5): 367-376, 2012.
Artigo em Inglês | LILACS | ID: lil-687637

RESUMO

We investigated the behavioral effects induced by an acute exposure to a commercial formulation of glyphosate (GF) in a dose that was about double the concentration of the no observed adverse effect level (NOAEL) in male and female BALB/c mice. The acute neurotoxicity induced by GF exposure was determined through analysis of general activity, the sensory system, the psychomotor system, the central nervous system and the autonomous nervous system in both male and female mice. The behavioral effects on exploration, anxiety and depression induced by GF exposure were determined with the open field, elevated plus maze and tail suspension tests, respectively. GF induced few signs of acute neurotoxicity. Locomotion in the open field was decreased in only female mice. No signs of anxiety were detected in the plus maze test in both sex, however, a reduced exploration was observed in male mice in this apparatus. In the tail suspension test, both male and female mice showed an increased immobility time. No interaction between sex and treatment was detected. In conclusion, GF exposure at about a dose twice that of the NOAEL induced few signs of neurotoxicity and no sexual dimorphism in all behavioral models employed.


Neste trabalho investigou-se em camundongos BALB/c, machos e fêmeas, os efeitos comportamentais da exposição aguda a uma formulação comercial do glifosato (GF) em uma dose duas vezes maior que a dose sem efeito observado (NOAEL). A neurotoxicidade aguda ao GF foi determinada por meio da análise da atividade geral, de parâmetros sensoriais, psicomotores, do sistema nervoso central e autônomo em machos e fêmeas. Os efeitos exploratório, de ansiedade e depressão induzidos pelo GF foram observados no campo aberto, labirinto em cruz elevado e no teste da suspensão da cauda, respectivamente. O GF promoveu poucos sinais de neurotoxicidade. A capacidade exploratória de fêmeas foi reduzida no campo aberto. Nenhum sinal de ansiedade foi detectado tanto em machos como em fêmeas no labirinto em cruz elevado porém, notou-se redução da exploratória neste aparelho. No teste de suspensão da cauda tanto as fêmeas como machos mostraram aumento no tempo de imobilidade. Não foi observado neste caso interação entre sexo e tratamento. Concluiu-se que a exposição ao dobro da dose da NOAEL do GF induziu poucos sinais de neurotoxicidade e poucos efeitos sexualmente dimórficos em camundongos machos e fêmeas.


Assuntos
Animais , Comportamento Animal , Camundongos/classificação , Neurotoxinas/toxicidade , Caracteres Sexuais
9.
Psychol. neurosci. (Impr.) ; 3(2): 251-258, July-Dec. 2010. graf, tab
Artigo em Inglês | Index Psicologia - Periódicos | ID: psi-52260

RESUMO

Nepeta cataria (catnip) is a plant used in pet toys and to treat human diseases. Catnip has also been used in the treatment of some depressive disorders. In this paper, we studied the antidepressant, anxiogenic, and motor activity effects of acute and repeated feeding of chow enriched with 10 percent N. cataria leaves and the acute and repeated administration of apolar and polar extracts of N. cataria leaves in male mice. The results showed that repeated feeding and acute and repeated administration with the apolar extract reduced immobility in the behavioral despair test but did not alter elevated plus maze and open-field parameters. Acute feeding and the acute and repeated administration of the polar extracts of N. cataria leaves did not alter the behavior of mice. These data suggest that N. cataria has antidepressant properties. Moreover, this antidepressant activity was present in the apolar extract.(AU)


Assuntos
Animais , Camundongos , Comportamento Animal , Antidepressivos , Atividade Motora
10.
Psychol. neurosci. (Impr.) ; 3(2): 251-258, July-Dec. 2010. graf, tab
Artigo em Inglês | LILACS, Index Psicologia - Periódicos | ID: lil-604526

RESUMO

Nepeta cataria (catnip) is a plant used in pet toys and to treat human diseases. Catnip has also been used in the treatment of some depressive disorders. In this paper, we studied the antidepressant, anxiogenic, and motor activity effects of acute and repeated feeding of chow enriched with 10 percent N. cataria leaves and the acute and repeated administration of apolar and polar extracts of N. cataria leaves in male mice. The results showed that repeated feeding and acute and repeated administration with the apolar extract reduced immobility in the behavioral despair test but did not alter elevated plus maze and open-field parameters. Acute feeding and the acute and repeated administration of the polar extracts of N. cataria leaves did not alter the behavior of mice. These data suggest that N. cataria has antidepressant properties. Moreover, this antidepressant activity was present in the apolar extract


Assuntos
Animais , Comportamento Animal , Atividade Motora , Antidepressivos
11.
J. Health Sci. Inst ; 28(3): 289-294, july-sept. 2010. ilus
Artigo em Inglês | LILACS-Express | LILACS | ID: lil-606297

RESUMO

Objective - Nepeta cataria (catnip) is a plant used to treat human diseases and is also found in pet toys. This study was performed to analyze the anti-nociceptive and anti-inflammatory effects of N. cataria essential oil (NCEO) in female mice. Methods - Phytochemical analyses of NCEO were performed. In addition, female mice treated with the oil were observed in an open for its general activity and to investigate the dose and time responses. The anti-nociceptive effects were evaluated by tail immersion and acetic acid writhing reflex tests.The anti-inflammatory oil properties were investigated by the carrageenan-induced edema test. Results - The results showed that 0.0005 and 0.001 mL/kg i.p. doses of NCEO increased the general activity of female mice, and the 0.0005 mL/kg dose reduced their immobility. Moreover, NCEO (0.0005 mL/kg) has anti-nociceptive properties, as the treated animals exhibited an increased latency of tail withdrawal and reduced acetic acid-induced abdominal constrictions. Furthermore, NCEO (0.0005 mL/kg) presented peripheric anti-inflammatory properties by reducing the induced edema after carrageenan injection. Conclusions - These effects may be due to the nepetalactone trans-trans and trans-cis nepetalactone isomers, which were detected as the predominant active components in the phytochemical analysis. It was suggested that the main effect of NCEO occurs on the central nervous system mechanism of pain.


Objetivo - A Nepeta cataria (catnip) é uma planta utilizada para tratar doenças humanas e também é encontrada em brinquedos de animais de estimação. O objetivo deste estudo foi analisar os efeitos antinociceptivos e anti-inflamatório do óleo essencial de N. cataria (NCEO) em camundongos fêmeas. Métodos - A análise fitoquímica do NCEO foi realizada. Além disso, os animais que foram tratados como óleo e foram observados em um campo aberto para mensurar a sua atividade em geral e investigar a dose e tempo de respostas. Os efeitos antinociceptivos foram avaliados pelos testes de imersão da cauda e reflexo de contorções abdominais causadas pelo ácido acético. As propriedades anti-inflamatórias do óleo foram investigadas pelo teste de edema induzido por carragenina. Resultados - Os resultados mostraram que 0,0005 e 0,001mL/ kg doses ip. de NCEO aumentou a atividade geral de camundongos fêmeas, e dose de 0,0005 mL/kg reduziu sua imobilidade. Além disso, NCEO (0,0005 mL/kg), tem propriedades antinociceptiva, como os animais tratados apresentaram uma maior latência de retirada de cauda e reduziu as contorções abdominais induzidas pelo ácido acético. Além disso, NCEO (0,0005mL/kg) apresentou efeito periférico e propriedades anti-inflamatórias, reduzindo o edema induzido após a injeção de carragenina. Conclusões - Estes efeitos podem ser devido aos isômeros nepetalactone trans-trans e nepetalactone trans-cis, que foram detectados como os componentes ativos predominante na análise fitoquímica. Foi sugerido que o principal efeito da NCEO ocorre no mecanismo do sistema nervoso central da dor.

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