RESUMO
Behavioral sensitization is a process of neuroadaptation characterized by a gradual increase in motor behaviors. The major neural substrates involved in the behavioral sensitization lie on the dopaminergic mesocorticolimbic pathway, which is still under development during adolescence. To investigate age-differences in ethanol behavioral sensitization and dopamine levels in distinct brain regions of the reward system, adolescent and adult mice were repeatedly pretreated with saline or ethanol (2.0 g/kg i.p.) during 15 consecutive days and challenged with saline or ethanol 5 days after pretreatment. Dopamine and its metabolites were measured in tissue samples of the prefrontal cortex (PFC), nucleus accumbens (NAc) and striatum by HPLC analysis. While repeated ethanol administration resulted in the development of locomotor sensitization in both adult and adolescent mice, only the adults expressed sensitization to a subsequent ethanol challenge injection. Neurochemical results showed reduced dopamine levels in adolescents compared to adults. Specifically, mice pretreated with ethanol during adolescence displayed lower dopamine levels in the PFC compared to the respective adult group in response to an ethanol challenge injection, and preadolescent mice exhibited lower dopamine levels in the NAc following an acute ethanol treatment compared to adults. These findings suggest that adolescent mice are not only less sensitive to the expression of ethanol-induced sensitization than adults, but also show lower dopamine content after ethanol exposition in the PFC and NAc.
RESUMO
The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.
RESUMO
Heat stress has been related to the impairment of behavioral and immunological parameters in broiler chickens. However, the literature is not clear on the involvement of neuroimmune interactions in a heat stress situation associated with bacterial and parasitic infections. The present study evaluated the production of monoamines and their metabolites in brain regions (rostral pallium, hypothalamus, brain stem, and midbrain) in broiler chickens submitted to chronic heat stress and/or infection and co-infection with Eimeria spp. and Clostridium perfringens type A. The heat stress and avian necrotic enteritis (NE) modulated the neurochemical profile of monoamines in different areas of the central nervous system, in particular, those related to the activity of the hypothalamus-hypophysis-adrenal (HPA) axis that is responsible for sickness behavior. C. perfringens and/or Eimeria infection, heat stress increased 5-hydroxytryptamine (5-HT), 4,4 dihydroxyphenylacetic acid (DOPAC), and DOPAC/dopamine (DA) in the rostral pallium; 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), homovanillic acid (HVA), HVA/DA, DOPAC/DA, and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT in the hypothalamus; MHPG, 5-HIAA/5-HT, DOPAC/DA, and HVA/DA in the midbrain; and MHPG, DOPAC, HVA, HVA/DA, DOPAC/DA, and 5-HIAA/5-HT in the brainstem. Heat stress decreased noradrenaline + norepinephrine (NOR + AD) in all brain regions analyzed; 5-HT in the hypothalamus, midbrain, and brainstem; and DA in the midbrain. The results also showed the existence and activity of the brain-gut axis in broiler chickens. The brain neurochemical profile and corticosterone production are consistent with those observed in chronic stressed mammals, in animals with sickness behavior, and an overloading of the HPA axis.
RESUMO
Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice.
Assuntos
Proteínas de Membrana/genética , Mutação/genética , Neurotransmissores/metabolismo , Membrana dos Otólitos/patologia , Doenças Vestibulares/genética , Animais , Comportamento Exploratório/fisiologia , Elevação dos Membros Posteriores , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Atividade Motora , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , Aprendizagem Espacial , Natação , Doenças Vestibulares/etiologiaRESUMO
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.
RESUMO
We analysed the effects of cold stress (19 ± 1°C, 6â h /day, from the first to the seventh day of life) applied to specific pathogen free (SPF) chickens. On experimental Day 1 (ED1), chicks were divided into four groups: C (not infected and kept under thermoneutral condition); CS (not infected and cold stressed); PC (Salmonella Heidelberg (SH) infected and kept under thermoneutral condition) and PCS (SH infected and cold stressed). High concentrations of corticosterone were found in the cold stressed birds on ED7 and ED21, with a greater increase in birds of the PCS group. Stress or non-stressed SH-infected birds had high levels of norepinephrine on ED21. On ED21, an increased percentage and number of SH were found in birds of the PCS group. On ED7, a decrease in macrophages presenting MHCII, CD8(+) and CD8(+) γδ cells was observed in the chickens of the CS group. Decrease was observed in CD3(+) cells in the birds of the PCS group and increase in macrophages presenting MHCII cells and of the CD4(+)/CD8(+) ratio in chickens of the CS group on ED21. There was a decrease in CD8(+) γδ cells in birds of the CS group on ED21 and in the CD3(+) and CD8(+)cell numbers in chickens of the PCS group on ED21. Our results suggest that cold stress applied to chickens in the first 7 days of life increases both the hypothalamus pituitary adrenal axis and the sympathetic nervous system activities, leading to long-term immune cell dysfunction, thus allowing increased SH invasion and persistence within the birds' body.
Assuntos
Galinhas/imunologia , Doenças das Aves Domésticas/imunologia , Salmonelose Animal/imunologia , Salmonella/imunologia , Animais , Carga Bacteriana , Catecolaminas/sangue , Galinhas/microbiologia , Temperatura Baixa , Corticosterona/sangue , Imunidade , Macrófagos/imunologia , Doenças das Aves Domésticas/microbiologia , Salmonella/isolamento & purificação , Salmonelose Animal/microbiologia , Organismos Livres de Patógenos Específicos , Estresse FisiológicoRESUMO
Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Neurotransmissores/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Alcaloides de Pirrolizidina/farmacologia , Fatores Etários , Alanina Transaminase/sangue , Animais , Antineoplásicos Fitogênicos/química , Aspartato Aminotransferases/sangue , Proteínas Sanguíneas/metabolismo , Catalepsia/induzido quimicamente , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Alcaloides de Pirrolizidina/química , Ratos , Ratos Wistar , Fatores Sexuais , Comportamento Estereotipado/efeitos dos fármacos , Natação/psicologia , gama-Glutamiltransferase/sangueRESUMO
O terço distal do rádio e da ulna dos cães é o local mais acometido por fraturas em membros torácicos, devido à proporção elevada de tecido esponjoso nessa região. Durante o período de janeiro de 2005 a setembro de 2010, 54 animais receberam diagnóstico de fratura distal de rádio e ulna, mas em somente 27 deles houve acompanhamento. Os outros 27 animais interromperam o acompanhamento em um período muito precoce, por motivos relacionados aos proprietários. Foram analisados, por meio de fichas clínicas e exames radiográficos: o tempo médio de formação do calo ósseo, as principais complicações ocorridas durante sua evolução e se houve diferença significativa no tempo de consolidação dessas fraturas em cães de diferentes portes e idades. Por meio dos resultados estatísticos, pode-se concluir que a média para a consolidação das fraturas distais de rádio e ulna foi menor em cães com até um ano, e maior nos cães de raça de pequeno porte. A complicação mais observada neste estudo foi a não união atrófica, presente em 100% das complicações por não união.
The distal radius and ulna are the most affected parts in cases of thoracic limb fracture in dogs due to the high proportion of spongy tissue in this body region. Between January, 2005 and September, 2010, 54 animals were diagnosed with fractures of the distal radius and ulna, but only 27 were followed. The remaining 27 animals had the follow-up activity prematurely interrupted due to reasons related to the respective owners. Medical records and radiographic examinations were analyzed as regards the average time to callus formation, major complications during healing and whether there were significant differences in the healing time of these fractures in dogs of different sizes and ages. Statistical analysis indicates that the average healing time was shorter in dogs up to one year old and longer in small pure-bread dogs. The most common complication observed in this study was the atrophic non union, since it was present in 100% of the complications of non union.
El tercio distal del radio y cubito de los perros es la región con mayor presentación de fracturas en miembros anteriores, debido a una alta proporción de tejido esponjoso presente en ese local. Entre enero de 2005 y septiembre de 2012, se atendieron 54 animales con diagnóstico de fractura distal de radio y cúbito, de los que apenas 27 pudieron ser evaluados a largo plazo. Los otros 27 animales interrumpieron el seguimiento clínico en forma precoz debido a motivos relacionados con los propietarios. A través de fichas clínicas y exámenes radiográficos, fueron analizados el tiempo promedio de formación del callo óseo, las principales complicaciones durante su evolución y si hubo diferencia significativa entre el tiempo de consolidación de las fracturas y el tamaño y edad de los perros. Mediante análisis estadísticos se pudo concluir que el tiempo promedio de consolidación de las fracturas distales de radio y cúbito fue menor en perros de hasta un año de edad, y mayor en perros de razas de pequeño porte. La complicación mas observada en este estudio fue la unión atrófica, que estuvo presente en el 100% de los animales con no unión.
Assuntos
Animais , Fraturas Ósseas/veterinária , Radiografia/veterinária , Tecido Nervoso , Cães/classificaçãoRESUMO
O terço distal do rádio e da ulna dos cães é o local mais acometido por fraturas em membros torácicos, devido à proporção elevada de tecido esponjoso nessa região. Durante o período de janeiro de 2005 a setembro de 2010, 54 animais receberam diagnóstico de fratura distal de rádio e ulna, mas em somente 27 deles houve acompanhamento. Os outros 27 animais interromperam o acompanhamento em um período muito precoce, por motivos relacionados aos proprietários. Foram analisados, por meio de fichas clínicas e exames radiográficos: o tempo médio de formação do calo ósseo, as principais complicações ocorridas durante sua evolução e se houve diferença significativa no tempo de consolidação dessas fraturas em cães de diferentes portes e idades. Por meio dos resultados estatísticos, pode-se concluir que a média para a consolidação das fraturas distais de rádio e ulna foi menor em cães com até um ano, e maior nos cães de raça de pequeno porte. A complicação mais observada neste estudo foi a não união atrófica, presente em 100% das complicações por não união.(AU)
The distal radius and ulna are the most affected parts in cases of thoracic limb fracture in dogs due to the high proportion of spongy tissue in this body region. Between January, 2005 and September, 2010, 54 animals were diagnosed with fractures of the distal radius and ulna, but only 27 were followed. The remaining 27 animals had the follow-up activity prematurely interrupted due to reasons related to the respective owners. Medical records and radiographic examinations were analyzed as regards the average time to callus formation, major complications during healing and whether there were significant differences in the healing time of these fractures in dogs of different sizes and ages. Statistical analysis indicates that the average healing time was shorter in dogs up to one year old and longer in small pure-bread dogs. The most common complication observed in this study was the atrophic non union, since it was present in 100% of the complications of non union.(AU)
El tercio distal del radio y cubito de los perros es la región con mayor presentación de fracturas en miembros anteriores, debido a una alta proporción de tejido esponjoso presente en ese local. Entre enero de 2005 y septiembre de 2012, se atendieron 54 animales con diagnóstico de fractura distal de radio y cúbito, de los que apenas 27 pudieron ser evaluados a largo plazo. Los otros 27 animales interrumpieron el seguimiento clínico en forma precoz debido a motivos relacionados con los propietarios. A través de fichas clínicas y exámenes radiográficos, fueron analizados el tiempo promedio de formación del callo óseo, las principales complicaciones durante su evolución y si hubo diferencia significativa entre el tiempo de consolidación de las fracturas y el tamaño y edad de los perros. Mediante análisis estadísticos se pudo concluir que el tiempo promedio de consolidación de las fracturas distales de radio y cúbito fue menor en perros de hasta un año de edad, y mayor en perros de razas de pequeño porte. La complicación mas observada en este estudio fue la unión atrófica, que estuvo presente en el 100% de los animales con no unión.(AU)
Assuntos
Animais , Fraturas Ósseas/veterinária , Tecido Nervoso , Radiografia/veterinária , Cães/classificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system. MATERIALS AND METHODS: The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT(1A) receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment. RESULTS: The present work found anxiolytic-like activity of the EO at the dose of 10mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LDB, indicating that the EO activity occurs via the GABA(A) receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus. CONCLUSIONS: The results corroborate the use of Cymbopogon citratus in folk medicine and suggest that the anxiolytic-like effect of its EO is mediated by the GABA(A) receptor-benzodiazepine complex.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Cymbopogon , Agonistas de Receptores de GABA-A/farmacologia , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Ansiolíticos/química , Ansiolíticos/isolamento & purificação , Ansiedade/metabolismo , Ansiedade/psicologia , Cymbopogon/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Flumazenil/farmacologia , Moduladores GABAérgicos/farmacologia , Agonistas de Receptores de GABA-A/química , Agonistas de Receptores de GABA-A/isolamento & purificação , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Piperazinas/farmacologia , Folhas de Planta , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Plantas Medicinais , Piridinas/farmacologia , Antagonistas da Serotonina/farmacologia , Sono/efeitos dos fármacosRESUMO
Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical defects in both dams and pups. The present study evaluated male rats prenatally treated with LPS for behavioral and neurological effects related to the olfactory system, which is the main sensorial path in rodents. Pregnant Wistar rats received 100 µg/kg of LPS intraperitoneally (i.p.) on gestational day (GD) 9.5, and maternal behavior was evaluated. Pups were evaluated for (1) maternal odor preference, (2) aversion to cat odor, (3) monoamine levels and turnover in the olfactory bulb (OB) and (4) protein expression (via immunoblotting) within the OB dopaminergic system and glial cells. Results showed that prenatal LPS exposure impaired maternal preference and cat odor aversion and decreased dopamine (DA) levels in the OB. This dopaminergic impairment may have been due to defects in another brain area given that protein expression of the first enzyme in the DA biosynthetic pathway was unchanged in the OB. Moreover, there was no change in the protein expression of the DA receptors. The fact that the number of astrocytes and microglia was not increased suggests that prenatal LPS did not induce neuroinflammation in the OB. Furthermore, given that maternal care was not impaired, abnormalities in the offspring were not the result of reduced maternal care.
Assuntos
Lipopolissacarídeos/toxicidade , Percepção Olfatória/efeitos dos fármacos , Transtornos da Percepção/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Monoaminas Biogênicas/metabolismo , Antígeno CD11b/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Comportamento Materno/efeitos dos fármacos , Odorantes , Bulbo Olfatório/metabolismo , Transtornos da Percepção/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Receptores Dopaminérgicos/metabolismoRESUMO
Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical injuries in both the mother and pups. Previous investigations by our group showed that prenatal LPS administration (100 microg/kg, i.p.) on gestational day 9.5 impaired the male offspring's social behavior in infancy and adulthood. In the present study, we investigated whether these social behavioral changes were associated with motor activity impairment. Male rat pups treated prenatally with LPS or not were tested for reflexological development and open field general activity during infancy. In adulthood, animals were tested for open field general activity, haloperidol-induced catalepsy and apomorphine-induced stereotypy; striatal dopamine levels and turnover were also measured. Moreover, LPS-treated or untreated control pups were challenged with LPS in adulthood and observed for general activity in the open field. In relation to the control group, the motor behavior of prenatally treated male pups was unaffected at basal levels, both in infancy and in adulthood, but decreased general activity was observed in adulthood after an immune challenge. Also, striatal dopamine and metabolite levels were decreased in adulthood. In conclusion, prenatal LPS exposure disrupted the dopaminergic system involved with motor function, but this neurochemical effect was not accompanied by behavioral impairment, probably due to adaptive plasticity processes. Notwithstanding, behavioral impairment was revealed when animals were challenged with LPS, resulting in enhanced sickness behavior.
Assuntos
Encéfalo/crescimento & desenvolvimento , Lipopolissacarídeos/imunologia , Atividade Motora/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Apomorfina/farmacologia , Encéfalo/imunologia , Catalepsia/induzido quimicamente , Dopamina/metabolismo , Agonistas de Dopamina , Antagonistas de Dopamina , Comportamento Exploratório/fisiologia , Feminino , Desenvolvimento Fetal , Haloperidol , Locomoção/fisiologia , Masculino , Neostriado/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Ratos , Ratos Wistar , Reflexo , Fatores Sexuais , Estatísticas não Paramétricas , Comportamento Estereotipado/efeitos dos fármacosRESUMO
A great number of studies on scorpion venoms associate their effects to the autonomic nervous system, and few data are available about their action on the central nervous system (CNS). The aim of this work was to evaluate some central effects after intraperitoneal injection of Tityus serrulatus or T. bahiensis scorpion venoms. The hippocampal concentration of some neurotransmitters and their metabolites were determined. Electroencephalographic and behavioral observations were performed, and all brains were removed for histopathological analysis of hippocampal areas. Both venoms induced electrographic and behavioral alterations despite T. bahiensis venom affects less the electrographic activity than T. serrulatus venom. Neurochemical analysis demonstrated no alteration in the extracellular levels of almost all the neurotransmitters evaluated, at least in the hippocampus, and no neuronal loss in this area was observed. Meanwhile, extracellular concentration of HVA increased up to 10 times in approximately 1/3 of the animals of both groups. Scorpion venoms seem to exert a small but important central effect. More studies in this field are necessary because they may be useful in developing new strategies to reduce the damage caused by scorpion stings.
Assuntos
Encéfalo/efeitos dos fármacos , Venenos de Escorpião/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Aminoácidos/metabolismo , Animais , Monoaminas Biogênicas/metabolismo , Encéfalo/metabolismo , Eletroencefalografia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Microdiálise , Neurotransmissores/metabolismo , Ratos , Ratos WistarRESUMO
The present study investigated the effects of t moxidectin (MXD) in some parameters of rat motor function and neurochemical. The general activity in the open field and the motor coordination in the wooden beam were employed to evaluate the MXD effects. The results showed that, in the open field, even at high doses (2.0 and 20.0 mg/kg), the MXD did not alter the locomotion and the rearing frequencies. However, MXD was able to impair the motor coordination of the animals at wooden beam. Neurochemical studies of striatal GABA and dopamine neurotransmitters showed a reduced levels of dopamine and its metabolite, homovanillic acid, without interference on striatal GABA levels. Since GABAergic receptor stimulation had an inhibitory effect on dopaminergic striatal system, the decreased motor coordination could be attributed to an action of MXD on dopamine system via GABA activation.
A moxidectina (MXD) é uma droga antiparasitária amplamente empregada em animais domésticos; seu mecanismo de ação, em mamíferos, envolve o neurotransmissor ácido gama-aminobutírico (GABA). Esse neurotransmissor tem papel importante na função motora. Assim, no presente trabalho estudaram-se os efeitos da MXD em alguns parâmetros comportamentais ligados a função motora de ratos e também em sistemas de neurotransmissão central. A atividade geral no campo aberto e a coordenação motora na trave elevada foram empregadas para avaliar os efeitos de diferentes doses de MXD. Os resultados mostraram que: no campo aberto, mesmo as doses maiores (2.0 e 20.0 mg/kg) de MXD não alteraram as freqüências de locomoção e levantar. Por outro lado, a MXD foi capaz de prejudicar a coordenação motora dos animais avaliada na trave elevada. Estudos neuroquímicos dos níveis estriatais de GABA e dopamina mostraram redução dos níveis de dopamina e seu metabólito, ácido homavanílico, sem interferência nos níveis de GABA estriatal. Considerando que a estimulação de receptores GABAérgicos tem efeito inibidor sobre o sistema dopaminérgico estriatal, nós atribuímos a redução na coordenação motora a ação da MXD sobre o sistema dopaminérgico via ativação do GABA.
RESUMO
The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The mechanism of action, in mammals, involves GABA, a neurotransmitter with an important role in the sexual behavior control. Presently, the effects of 0.2 mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile erection and central GABA levels. Sexual behavior results showed increased latencies to the first mount and intromission as well as in inter-intromission interval; a reduction in total mounts was detected on the drug post-treatment. No difference was observed between sexual motivation of control and experimental animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The results suggest that MXD reduced sexual behavior and penile erection by an action on the hypothalamic GABA system. Probably, the lack of effects in the motivational test and the increased mount and intromission latencies as well as decreased total mounts could be explained as a consequence of reduced male rat erection process.
Assuntos
Anti-Helmínticos/efeitos adversos , Hipotálamo/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Feminino , Hipotálamo/metabolismo , Macrolídeos/efeitos adversos , Masculino , RatosRESUMO
The objective of the present study was to implant a method using asensitive and specific system, and validate the whole analytical method to obtain an efficient tool for analyses of tramadol in plasma dogs,and to evaluate the pharmacokinetics of tramadol following intravenous (i.v.) and intramuscular (i.m.) administration of this drug in females dogs submitted to castration. The pharmacokinetics of tramadol were examined following i.v. or i.m. tramadol administration to five female dogs in each group submitted to ovariohysterectomy(dosage=2 mg/kg). In relation to intravenous administration, the half-time for the distribution process (t1/2d = 0.18 ± 0.12 h); the total body clearance was 0.60 ± 0.50 L/h/kg, half-life of elimination (t1/2b)was 1.24 ± 0.69 h. Statistically differences between parameters obtained after i.v. and i.m. was significant only to AUC0∞: 3362.07 ± 1008 and 1604.55 ± 960.02 (ng.h/mL), respectively. The F was 48.00 ± 43.30 %. The assay for tramadol described has been demonstrated to meet all requirements for clinical PK studies. In particular, the method has satisfactory specificity, linearity, accuracy and precision range over the concentration examined.(AU)
O objetivo do presente estudo foi de implantar um método sensível e específico, e validar toda a metodologia para obter uma ferramenta eficiente para a análise do tramadol em plasma de cadelas, e avaliar a farmacocinética do tramadol após a administração do mesmo pelas vias i.v. e i.m. em cadelas submetidas à castração. A farmacocinética do tramadol foi examinada após a administração do tramadol por ambas as vias, em cinco cadelas em cada grupo submetidas à ovário histerectomia (dose = 2 mg/kg). Em relação à administração intravenosa, a meia-vida de eliminação (t1/2b) foi de 1,24 ± 0,69 h. Encontrou-se diferenças significantes somente nos parâmetros AUC0∞: 3362,07 ± 1008 and 1604,55 ± 960.02 (ng.h/mL), pelas vias i.v. e i.m. respectivamente. O F foi de 48,00 ± 43,30 %. O estudo descrito neste artigo demonstrou atingir todas as exigências para os estudos clínicos em farmacocinética. Especificamente, o método apresentou especificidade, linearidade, exatidão e precisão satisfatórias no intervalo de concentrações examinadas.(AU)
Assuntos
Animais , Tramadol/análise , Farmacocinética , Castração/métodos , Histerectomia/métodos , CãesRESUMO
The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The mechanism of action, in mammals, involves GABA, a neurotransmitter with an important role in the sexual behavior control. Presently, the effects of 0.2 mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile erection and central GABA levels. Sexual behavior results showed increased latencies to the first mount and intromission as well as in inter-intromission interval; a reduction in total mounts was detected on the drug post-treatment. No difference was observed between sexual motivation of control and experimental animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The results suggest that MXD reduced sexual behavior and penile erection by an action on the hypothalamic GABA system. Probably, the lack of effects in the motivational test and the increased mount and intromission latencies as well as decreased total mounts could be explained as a consequence of reduced male rat erection process.
Assuntos
Masculino , Animais , Ratos , GABAérgicos , Receptores de GABA , Comportamento Sexual , Ereção PenianaRESUMO
The objective of the present study was to implant a method using asensitive and specific system, and validate the whole analytical method to obtain an efficient tool for analyses of tramadol in plasma dogs,and to evaluate the pharmacokinetics of tramadol following intravenous (i.v.) and intramuscular (i.m.) administration of this drug in females dogs submitted to castration. The pharmacokinetics of tramadol were examined following i.v. or i.m. tramadol administration to five female dogs in each group submitted to ovariohysterectomy(dosage=2 mg/kg). In relation to intravenous administration, the half-time for the distribution process (t1/2d = 0.18 ± 0.12 h); the total body clearance was 0.60 ± 0.50 L/h/kg, half-life of elimination (t1/2b)was 1.24 ± 0.69 h. Statistically differences between parameters obtained after i.v. and i.m. was significant only to AUC0∞: 3362.07 ± 1008 and 1604.55 ± 960.02 (ng.h/mL), respectively. The F was 48.00 ± 43.30 %. The assay for tramadol described has been demonstrated to meet all requirements for clinical PK studies. In particular, the method has satisfactory specificity, linearity, accuracy and precision range over the concentration examined.
O objetivo do presente estudo foi de implantar um método sensível e específico, e validar toda a metodologia para obter uma ferramenta eficiente para a análise do tramadol em plasma de cadelas, e avaliar a farmacocinética do tramadol após a administração do mesmo pelas vias i.v. e i.m. em cadelas submetidas à castração. A farmacocinética do tramadol foi examinada após a administração do tramadol por ambas as vias, em cinco cadelas em cada grupo submetidas à ovário histerectomia (dose = 2 mg/kg). Em relação à administração intravenosa, a meia-vida de eliminação (t1/2b) foi de 1,24 ± 0,69 h. Encontrou-se diferenças significantes somente nos parâmetros AUC0∞: 3362,07 ± 1008 and 1604,55 ± 960.02 (ng.h/mL), pelas vias i.v. e i.m. respectivamente. O F foi de 48,00 ± 43,30 %. O estudo descrito neste artigo demonstrou atingir todas as exigências para os estudos clínicos em farmacocinética. Especificamente, o método apresentou especificidade, linearidade, exatidão e precisão satisfatórias no intervalo de concentrações examinadas.
Assuntos
Animais , Castração/métodos , Cães , Histerectomia/métodos , Farmacocinética , Tramadol/análiseRESUMO
The present study evaluated the central monoamine levels of male and female adult rat offspring exposed orally by gavage to 0.0, 0.7, 3.0 and 15.0 mg/kg I. carnea aqueous extract daily, from gestation day (GD) 5 to GD 21. Several alterations in the monoamine activity systems were observed. However, the major differences were noted between the 0.0 mg/kg and the no gavage control groups, showing that alterations showing that alterations were not due to the alterations to the aqueous extract. The control data showed that gavage and handling of dams were stressful enough to produce a significant decline in 3,4-dihydroxyphenylacetic acid (DOPAC) and an increase in vanilmandelic acid (VMA), indicating decreased dopamine (DA) and enhanced norepinephrine (NE) activity, respectively.
Estudo anterior realizado em filhotes de ratas tratadas diariamente por gavage com 0,0, 0,7, 3,0 e 15,0 mg/kg de uma solução aquosa obtida de folhas frescas da Ipomoea carnea, do dia 5 ao dia 21 da gestação, mostrou poucas alterações comportamentais na prole em vida adulta. O presente estudo teve como objetivo avaliar a atividade e níveis das monoaminas cerebrais nas proles masculina e feminina expostas ao mesmo tratamento acima descrito. As maiores alterações encontradas, entretanto, foram entre os grupos 0,0 mg/kg e controle negativo (no gavage), impedindo a atribuição das alterações encontradas à solução aquosa. O dados resultantes do grupo controle sugerem que o estresse provocado pela gavage e pelo manuseio das fêmeas enquanto prenhes é suficiente para produzir um importante declínio nos níveis do ácido 3,4 dihidroxifenilacético (DOPAC) e um não menos importante aumento nos níveis do ácido vanilmandélico (VMA), promovendo maior atividade do sistema noradrenérgico (NE).
RESUMO
The present study was designed to evaluate the effects of cohabitation for 11 days with a sick conspecific on hypothalamic levels and turnover of noradrenaline NA (experiment 1) and on neutrophil oxidative burst and phagocytosis in mice (experiment 2). Female mice were divided into two groups: control and experimental. One mouse of each control pair was kept undisturbed and called "companion of health partner" (CHP). One animal of each experimental pair of mice was inoculated with 5 x 10(6) Ehrlich tumor cells i.p., and the other, the subject of this study, was called "companion of sick partner" (CSP). In experiment 3, CHP and CSP mice were treated with diazepam (1.0 mg/kg) or with control solution (vehicle of diazepam, 1.0 mL/kg) 1h before evaluation of neutrophil activity. The CSP mice presented (1) decreased levels and increased turnover of hypothalamic NA; (2) decreased neutrophil oxidative burst after PMA or Staphylococcus aureus induction; (3) decreased percentage and intensity of neutrophil phagocytosis. In CSP mice, diazepam induced no changes in neutrophil oxidative burst or intensity of phagocytosis, but abolished almost completely the percentage of neutrophils performing phagocytosis. These data were discussed in the light of possible neuroimmune interactions.