Role of environmental enrichment on social interaction, anxiety, locomotion, and memory in Wistar rats under chronic methylphenidate intake.

Introduction: Chronic use of various compounds can have long-lasting effects on animal behavior, and some of these effects can be influenced by the environment. Many environmental enrichment protocols have the potential to induce behavioral changes. Aim: The aim of the present study was to investigate how environmental enrichment can mitigate the effects of chronic methylphenidate consumption on the behavior of Wistar rats. Methods: The animals were housed for 20 days under either an environmental enrichment protocol (which included tubes of different shapes) or standard housing conditions. After seven days, half of the rats received 13 days of oral administration of methylphenidate (2 mg/kg). After seven days, the rats underwent behavioral tests, including the elevated plus maze (anxiety), open field (locomotion), object-in-place recognition test (spatial memory), and a test for social interaction (social behavior). Results: The results showed that the enriched environmental condition reversed the enhanced time in the open arms of the elevated plus maze induced by methylphenidate (F[1,43] = 4.275, p = 0.045). Methylphenidate also enhanced exploratory rearing in the open field (F[1,43] = 4.663, p = 0.036) and the time spent in the open area of the open field (H[3] = 8.786, p = 0.032). The enriched environment mitigated the inhibition of social interaction with peers induced by methylphenidate (H[3] = 16.755, p < 0.001) as well as the preference for single exploratory behavior (H[3] = 9.041, p = 0.029). Discussion: These findings suggest that environmental enrichment can counteract some of the effects of methylphenidate. These results are relevant for the clinical treatment of the long-lasting secondary effects associated with methylphenidate pharmacological treatment.

Providing Environmental Enrichment without Altering Behavior in Male and Female Wistar Rats (Rattus norvegicus).

In research using animal models, subjects are commonly maintained under standard housing conditions, mainly because of the idea that enhancing welfare conditions could alter experimental data. Another common practice in many laboratories relates to the preponderant use of males. Several reasons justifying this practice include the rapid hormonal and endocrine change in females, which may require a higher number of female animals to achieve more homogenous groups, thereby creating a dilemma with the reduction principle in animal research. In past decades, a relationship between enriched environments and enhanced cognitive functions has been reported in rats, but many of those enriched environmental protocols were not systematically or rigorously studied, leading to unexpected effects on behavior. Here we report the effects of 4 types of housing conditions (standard, structural changes, exercise, and foraging) in Wistar rats on anxiety (elevated plus maze), exploratory (open field), and stress vulnerability (forced swim test) responses. Sex was used as a blocking factor. Data show no effect of housing conditions on anxiety and exploratory behaviors, but do show an effect on stress responses. These results suggest the possibility of using a protocol for environmental enrichment without concern about altering experimental data. From this stand, new ways to enhance animal welfare in research laboratories could be designed and implemented.

Cathodal transcranial direct current stimulation on the prefrontal cortex applied after reactivation attenuates fear memories and prevent reinstatement after extinction.

BACKGROUND: In the last decade, pharmacological strategies targeting reconsolidation after memory retrieval have shown promising efforts to attenuate persistent memories and overcome fear recovery. However, most reconsolidation inhibiting agents have not been approved for human testing. While non-invasive neuromodulation can be considered an alternative approach to pharmacological treatments, there is a lack of evidence about the efficacy of these technologies when modifying memory traces via reactivation/reconsolidation mechanism. OBJECTIVE: In this study, we evaluate the effect of cathodal (c-tDCS) and anodal (a-DCS) transcranial direct current stimulation applied after memory reactivation and extinction in rats. METHODS: Male Wistar rats were randomly assigned into three groups: one sham group, one anodal tDCS group, and one cathodal tDCS group (500 µA, 20 min). Reconsolidation and extinction of fear memories were evaluated using a contextual fear conditioning. RESULTS: Our results showed that c-tDCS and a-tDCS after memory reactivation can attenuate mild fear memories. However, only c-tDCS stimulation prevented both fear expression under strong fear learning and fear recovery after a reinstatement protocol without modification of learning rate or extinction retrieval. Nevertheless, the remote memories were resistant to modification through this type of neuromodulation. Our results are discussed considering the interaction between intrinsic excitability promoted by learning and memory retrieval and the electric field applied during tDCS. CONCLUSION: These results point out some of the boundary conditions influencing the efficacy of tDCS in fear attenuation and open new ways for the development of noninvasive interventions aimed to control fear-related disorders via reconsolidation.

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.

Neuro-«lo que sea¼: inicio y auge de una pseudociencia para el siglo XXI / Neuro-"whatever": Beginnings of a new pseudoscience for the XXI century

El paso del estado sésil al movimiento activo, requirió del desarrollo de un sistema nervioso capaz de coordinar el movimiento hacia fuentes de alimentación y el escape de posibles amenazas. En respuesta a los cambios en los ambientes macro- y micro-, los sistemas nerviosos fueron integrando habilidades cada vez mejores culminando en el «ensayo mental¼ (León & Cárdenas, 2011): el animal podía «imaginar¼ las consecuencias de algunas de sus acciones (causas y efectos), sin requerir ejecutarlas: la diferencia entre la vida y la muerte. Ya en los albores de la humanidad, esa necesidad imperiosa de buscar causas -ahora en una esfera plenamente mental- se plasmó en la creación de conceptualizaciones animistas de la naturaleza y por ello las primeras manifestaciones culturales fueron las explicaciones del universo en términos de mitos, leyendas, cuentos e historias transmitidas generacionalmente. El desarrollo de las tecnologías que fortalecían la unión cultural y las alianzas entre clanes, impulsó el desarrollo del conocimiento científico que mejoraba la tecnología y satisfacía más profundamente la sed de explicación del mundo. Fue la primera gran escisión entre ciencia y tecnología. Para el común, el impacto de la tecnología sobre la vida diaria es mucho más evidente que el de la ciencia, visión inmediatista que aún hoy rige, lastimosamente, a muchos organismos de gestión de la ciencia y la tecnología en muchos países. La separación ciencia (comprensible por pocos) / tecnología (usable por todos) hizo que paulatinamente se fuera desconociendo el real valor de la ciencia y permitió que muchas formas de conocimiento no científico, mucho más fácil de comprender y de transmitir -las «pseudociencias¼ (pseudo = que quiere ser, pero no es)- fueran instaurándose. Este conocimiento es «comprobado¼ por casos únicos que alguna vez sucedieron o que alguien reporto que vio o escucho (sin importar la veracidad del reporte). Ritos, mitos, magia, leyendas, alquimia y otras muchas ideas surgieron de esa forma.

Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats.

The role of serotonin (5-hydroxytryptamine [5-HT]) and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]). The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM). In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL) and prelimbic (PL) cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices. Highlights -CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.-CHF rats have a more "anxious" phenotype than CLF rats in the EPM.-The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.-Systemic and IL injections either decreased (CHF) or increased (CLF) anxiety-like behavior.-PL injections either decreased (CHF) anxiety-like behavior or had no effect (CLF).

Gerbils exhibit stable open-arms exploration across repeated testing on the elevated plus-maze.

Repeated testing on the elevated plus-maze (EPM) leads rats and mice to avoid the open-arms of the apparatus. The effect of multiple exposures to the EPM on the behavioral profile of gerbils is unknown. In this study, young and middle-aged gerbils were exposed to the EPM and four retests were carried out 24, 48, 72 and 96h after the first trial in order to determine whether animals exhibited open-arms avoidance. In addition, groups of young and middle-aged gerbils were exposed to the EPM for 20-min followed by a 5-min retest trial 24h apart to analyze the effect of a prolonged exposure to the EPM on open-arms exploration during first trial and retest. Gerbils exhibited high exploration of open-arms during the first trial and progressive locomotor decrease across repeated testing. Unlike previous reports for rats and mice, young gerbils showed a stable open-arms exploration both across multiple exposures and during a prolonged exposure to EPM. Middle-aged gerbils also exhibited a stable open-arms exploration during retest prior to the 20-min test. Results suggest a reliable repeated test paradigm for the EPM using our proposed methodology for gerbils.