Temporal and Spatial Characterization of Gait Pattern in Rodents as an Animal Model of Cerebrovascular Lesion / Caraterização Temporo - Espacial do Padrão de Marcha em Roedores como Modelo Animal de Lesão Cerebrovascular / Caracterización temporo-espacial del patrón de marcha en roedores como modelo animal de lesión cerebrovascular

RESUMEN En la investigación sobre movimiento, la experimentación animal ha proporcionado fundamentación científica para la investigación clínica, mejorando procedimientos diagnósticos y de rehabilitación. Lesiones cerebrales en roedores pueden ser usadas para modelar síntomas locomotores, sensoriales y/o cognitivos. Con el propósito de determinar la funcionalidad locomotriz y sensorial en roedores, se han propuesto varios métodos de evaluación y pronóstico clínico para identificar y evaluar adaptaciones estructurales y mecanismos de neuro-recuperación. Esto ha permitido que métodos de intervención terapéutica, como el ejercicio físico, sean utilizados para restaurar funciones sensitivo-motoras y cognitivas en roedores y humanos. La extrapolación (translación) de los resultados de investigaciones en ciencias básicas a áreas clínicas, supone la continua cooperación y retroalimentación entre investigadores y profesionales de la salud, favoreciendo la formulación de intervenciones terapéuticas más eficaces basadas en resultados obtenidos de la experimentación animal. El objetivo de esta revisión es exponer las principales deficiencias motoras y los métodos empleados para determinar la dificultad motriz en la marcha en roedores con lesión cerebrovascular, para lo cual se realizó una revisión de literatura, sobre términos definidos (MeSH), en las bases de datos PsychINFO, Medline y Web of Science, entre enero de 2000 y enero de 2017. Se excluyeron artículos de carácter cualitativo o narrativo, sin revisión por pares, disertaciones, tesis o trabajos de grado y resúmenes de conferencias. Se revisan algunas manifestaciones clínicas, su efecto en la locomotricidad en roedores, algunas metodologías usadas para generar lesiones y para estudiar la función motriz, los principales métodos de medición y algunos aspectos translacionales.

ABSTRACT Animal experimentation is crucial for the advance in the understanding of pathophysiological mechanisms and their application on both clinical diagnosis and neuro-rehabilitation. Particularly, rodent brain lesion is commonly used in the modeling of locomotor, somatosensory and cognitive symptoms. The automated rodent gait analysis has been proposed as a tool for studying locomotor and sensory abilities and its use includes the identification of functional alterations, structural adaptations as well as neuro-rehabilitation mechanisms. From that standpoint, the effectiveness of many therapeutic interventions (i.e. physical exercises) has been documented in rodents and humans. The translation from experimental data to clinical conditions requires the continuous collaboration and feedback between researchers and health clinicians looking for the selection of the best rehabilitation protocols obtained from animal research. Here we will show some locomotor alterations, the traditional methods used to assess motor dysfunction and gait abnormalities in rodent models with stroke. The aim of this review is to show some motor deficiencies and some methods used to establish gait disturbances in rodents with cerebrovascular lesion. The review included the search of defined terms (MeSH) in PychINFO, Medline and Web of Science, between January 2000 and January 2017. Qualitative and narrative reports, dissertations, end course works and conference resumes were discarded. The review focuses on some clinical signs, their effects on rodent locomotor activity, some methodologies used to create lesion and to study motor function, some assessment methods and some translational aspects.

RESUMO No estudo do movimento, a experimentação animal tem proporcionado sólida fundamentação científica para a pesquisa clínica, permitindo melhorar procedimentos diagnósticos e de reabilitação. Lesões cerebrais em roedores são utilizadas para modelar sintomas locomotores, sensoriais e cognitivos. Para determinar a funcionalidade locomotora e sensorial em roedores, têm sido desenvolvidas várias metodologias para avaliar o prognóstico clínico e identificar adaptações estruturais e mecanismos da recuperação. Todos esses achados têm favorecido que alguns métodos de intervenção terapêutica sejam utilizados para restaurar funções sensitivo-motoras e cognitivas em roedores e pacientes. A extrapolação (translação) de resultados de pesquisas em ciências básicas para as áreas clínicas, supõe a contínua cooperação e retroalimentação entre pesquisadores e profissionais da saúde, desenhando intervenções terapêuticas mais eficazes, baseadas em resultados obtidos na experimentação animal. Nesta revisão se expõem metodologias utilizadas para criar e avaliar alterações motoras, em modelos animais com acidente cerebral vascular. O objetivo é apresentar deficiências motoras e métodos utilizados para determinar a dificuldade na marcha em roedores com lesão cerebrovascular. Para isso foi feita uma revisão da literatura, usando termos definidos (MeSH), nas bases de dados PsychINFO, Medline e Web of Science, entre janeiro de 2000 e janeiro de 2017. Foram excluídos artigos qualitativos, narrativas, sem revisão por pares, dissertações, teses ou trabalhos de grado e resumos de palestras. Se revisam manifestações clínicas, seus efeitos na locomoção de roedores, algumas metodologias usadas para gerar lesões e para estudar a função motora, os principais métodos de medição e alguns aspectos translacionais.

Efecto de la aplicación aguda de fluoxetina sobre una tarea de miedo condicionado al contexto en ratas sometidas a restricción comportamental / Effect of acute Fluoxetine application on a context fear conditioned task in behaviorally restrained rats Laura A

Para estudiar el efecto del aumento comportamental o farmacológico de la ansiedad sobre la adquisición del miedo condicionado al contexto, 32 ratas Wistar (275±25 gm) divididas en dos grupos (restricción comportamental y control) recibieron fluoxetina (ig, 4 mg/kg; 1ml) o solución salina (ig, 0.9%). Luego fueron entrenadas en una tarea de miedo condicionado al contexto. El ANOVA de dos vías mostró diferencias significativas para el factor tratamiento (F[1,28] = 25.261; P < 0.001). Los sujetos tratados con fluoxetina presentaron menor tiempo de congelamiento (Student Newman-Keuls; P < 0.05). No hubo diferencias significativas para la restricción, ni para la interacción entre factores (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Así, la restricción no alteró la adquisición del miedo condicionado indicando que el aumento de liberación de 5-HT así inducido, no es comparable al inducido por fluoxetina. La fluoxetina deterioró la adquisición de la respuesta de miedo, indicando que el mecanismo por el cual la ansiedad interrumpe el aprendizaje puede ser serotoninérgico...

In order to study the effect of behavioral or pharmacologically enhanced anxiety on the acquisition of contextual fear conditioning, thirty two Wistar rats (275±25 gm) were divided in two groups (behavioral restriction and control). Half of each group received saline solution (ig.; 0.9%) or fluoxetine (ig.; 4mg/Kg) before the fear conditioning procedure. The two way ANOVA showed significant differences for treatment (F[1,28] = 25.261; P < 0.001). Student Newman-Keuls showed that subjects treated with fluoxetine had lower freezing times. There were no significant differences nor for restriction neither for the interaction between the factors (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Thus, the restriction procedure used did not modify the acquisition of the conditioned fear response suggesting that the putative 5-HT enhancement induced is not comparable to that induced by fluoxetine. Acute fluoxetine disrupted the acquisition of the conditioned fear response, suggesting that the mechanism by means of which anxiety disrupts learning could be serotonergic in nature...

Redundancia de la información visual en el condicionamiento aversivo: papel del colículo superior / Redundancy of visual information in aversive conditioning: role of the superior colliculus

Una característica de casi todos los sistemas biológicos es el procesamiento en paralelo o distribuido,el cual otorga al sistema una redundancia funcional que garantiza la permanencia de procesosincluso en ausencia de porciones del sistema. En el sistema visual existen tres vías que simultáneamentese encargan de varios aspectos de la percepción. El procesamiento realizado por la ramacolicular de este sistema está muy relacionado con los sistemas de valoración emocional límbicos,gracias a la vía colículo superior —núcleo suprageniculado— amígdala. En el presente trabajo seevaluó el efecto de la inactivación del colículo superior en la formación de un condicionamientoaversivo visual. Para esto ratas Wistar recibieron una microinyección intracolicular de lidocaína (1%)durante la adquisición del condicionamiento. Los resultados obtenidos mostraron claramente que elcolículo superior no es una estructura indispensable para la formación de tal condicionamiento, loque sugiere que otros sistemas de relevo subcortical deben estar implicados. A partir de ello esposible hipotetizar nuevas formas de aproximación al estudio de las características de redundanciafuncional en el sistema visual.

A relevant feature of biological systems is the distributed processing. This kind of informationprocessing ensures a functional redundancy that allows a functional level even in the absence ofsome regions of the system. In the case of visual system, the parallel processing relies on threesimultaneous pathways, each one of them carrying out certain aspects of visual information processing.The collicular branch of this parallel system is related to emotional aspects. This pathway transmitsinformation from the superior colliculus to the amygdala, via the suprageniculate nucleus. Here wetest the effect of the transient inhibition of the superior colliculus on the acquisition of a classicalaversive conditioning. Wistar rats received an intracollicular microinjection of lidocaine (1%)immediately before the training session. Our results clearly show that the superior colliculus is notthe main structure involved in the acquisition of this kind of associative learning suggesting thecontribution of other subcortical structures.

Contribution of the dopaminergic system to the effect of chronic fluoxetine in the rat forced swim test

Chronic administration of selective serotonin reuptake inhibitors (SSRI) enhances dopaminergic activity. However, the role of enhanced dopaminergic transmission in the therapeutic effects of this kind of antidepressants is still unclear. Drugs producing dopaminergic activation lead to an increment in general activity. Thus, it is reasonable to assume that some of the therapeutic effects of SSRIs are due to dopaminergic enhanced functionality. The forced swim test (FST) is a widely used test in the screening of new compounds with potential antidepressant activity. In this study the effects of pretreatment with low doses of the DA release inductor cocaine and the D2, D3 and D4 antagonist haloperidol were analyzed in the FST on rats submitted to chronic intragastric administration of the SSRI fluoxetine. Our results show that animals treated with fluoxetine and pre-treated with cocaine had significantly higher latencies than saline or haloperidol pre-treated subjects. Among both fluoxetine and saline treated animals, those pre-treated with cocaine had significant lesser immobility time. Haloperidol pre-treated animals had significantly higher immobility time than those pre-treated with saline. From these results, it is clear that the pharmacological modification of dopaminergic systems leads to behavioral changes in rats treated with both saline and fluoxetine. The FST does not have enough precision as to distinguish between dopaminergic and nondopaminergic components in the antidepressant effects of SSRIs, for this reason the use of the FST in combination to other models is mandatory.