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This study evaluated the long-term effect of biochar application on the sorption and desorption of thiamethoxam in a Haplic Plinthosol. The experiment was conducted in a randomized block design with combination of doses of mineral fertilizer NPK (0 and 300 kg·ha-1 formula 05-25-15) and biochar (0, 16 and 32 Mg ha-1). Deformed soil samples were collected in the field from the 0-0.10 m layer of all plots to determine the sorption and desorption of the thiamethoxam insecticide in the soil; fulvic acid (FA), humic acid (AH) and humin (HUM) carbon contents; and total organic carbon. The Batch slurry method was used to evaluate sorption and desorption. The Freundlich isotherm adequately described thiamethoxam sorption in all treatments. The application of biochar increased the sorption (Kfs) and decreased the desorption (Kfd) of thiamethoxam. The sorption intensity (1/n) showed reduction characteristics as the soil concentration of thiamethoxam increased. Biochar has a sorption effect on the soil through covalent bonds and H-bonds with the insecticide molecules, thereby indirectly increasing the sorption potential in the chemical fractions of the organic matter of soil. The application of 32 Mg ha-1 of biochar significantly reduced thiamethoxam in the soil solution. Altogether, the present study reveals that biochar application in soil is a promising tool for mitigating the contaminant potential of thiamethoxam in subsurface waters.
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Inseticidas , Poluentes do Solo , Adsorção , Carbono/química , Carvão Vegetal/química , Solo/química , Poluentes do Solo/análise , TiametoxamRESUMO
The interest in psychedelic substances as potential treatments for psychiatric disorders is increasing. The ß-carboline harmine, an Ayahuasca component, presents hallucinogenic and antidepressant effects. Although Ayuahuasca-and consequently harmine-is usually consumed in rituals, the role of social contexts in the behavioral effects of harmine has not been investigated yet. In this sense, affective states may modulate cohabitants' behavior, including learning/memory. This work investigates the effects of harmine on the learning/memory performance of rats evaluated on the contextual and tone fear conditioning (CFC and TFC) and on the plus-maze discriminative avoidance (PMDAT) tasks. The possible influence of a harmine-treated cohabitant was assessed by evaluating rats housed in homogeneous cages-where all the animals were acutely administered with the same treatment (vehicle, 5, 10, or 15 mg/kg harmine), and in heterogeneous cages-where each animal received a different drug treatment. The main results are: (a) harmine impaired CFC (10 mg/kg) and PMDAT discrimination (all doses); and (b) harmine caused a memory deficit in CFC, TFC, and PMDAT of untreated rats kept in heterogeneous cages. Our results show that harmine induces a memory deficit in tasks with emotional contexts. Further, the cohabitation with animals treated with this drug also seems to impair memory performance of untreated animals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Emoções , Harmina , Ratos , Animais , Harmina/farmacologia , Cognição , Medo , Transtornos da MemóriaRESUMO
Objetivo: Avaliar a cultura de segurança do paciente na perspectiva dos profissionais de saúde das unidades assistenciais de áreas críticas em um hospital universitário. Material e Método: Estudo observacional, seccional, de abordagem quantitativa, realizado com 207 profissionais de saúde, médicos, enfermeiros e técnicos em enfermagem de um hospital no estado de Minas Gerais, Brasil, no período de janeiro a novembro de 2020. Os participantes foram obtidos por meio de amostra não probabilística e responderam ao questionário Hospital Survey on Patient Safety Culture, instrumento já validado para a realidade brasileira. Empregaram-se análises estatística descritiva e de regressão linear múltipla; o nível de significância considerado foi α =0,05. Resultados: A dimensão melhor avaliada foi "Aprendizado Organizacional - melhoria contínua" (64,4%). Nenhuma dimensão foi considerada área forte por não receber pontuação ≥ 75%. Oito dimensões foram consideradas áreas frágeis (≤ 50%), sendo a dimensão "Respostas não punitivas aos erros" a pior avaliada (20,3%). A nota de segurança do paciente conferida pelo profissional em sua área de trabalho no hospital (β = 0,502; p< 0,001) e o tempo de trabalho no hospital (β = 0,135; p= 0,032) foram estatisticamente significativos quando associadas ao escore geral. Conclusão: O estudo permitiu identificar fragilidades dentro da instituição, sendo a resposta não punitiva aos erros a mais preocupante. Os líderes devem propor intervenções que propiciem um ambiente livre de culpa, para que os profissionais relatem os eventos adversos. Considerar a segurança do paciente como uma prioridade da gestão pode proporcionar melhor qualidade aos serviços oferecidos pela organização.
Objective: To assess patient safety culture from the perspective of health care professionals working in critical care units at a university hospital. Material and Method: Observational, sectional study, with a quantitative approach, conducted with 207 health professionals, doctors, nurses and nursing technicians from a hospital in the state of Minas Gerais, Brazil, from January to November 2020. The participants were obtained through a non-probabilistic sample and answered the Hospital Survey on Patient Safety Culture questionnaire, an instrument already validated for the Brazilian context. Descriptive statistical and multiple linear regression analyses were used; the significance level was α =0.05. Results: The best assessed dimension was "Organizational learning - continuous improvement" (64.4%). No dimension was considered particularly strong as it did not receive a score ≥ 75%. Eight dimensions were considered weak areas (≤ 50%), with the dimension "Non-punitive response to error" being the worst assessed (20.3%). The patient safety score given by the professional in their hospital working area (β=0.502, p<0.001) and the length of time working in the hospital (β=0.135, p=0.032) were statistically significant when associated with the overall score. Conclusions: This study makes it possible to identify weaknesses within the institution, with the non-punitive response to errors being the most concerning. Leaders should propose interventions that provide a blame-free environment for professionals to report adverse events. Considering patient safety as a management priority can provide better quality to the services offered by the organization.
Objetivo: Evaluar la cultura de seguridad del paciente desde la perspectiva de los profesionales de la salud que laboran en las unidades de cuidados críticos de un hospital universitario. Material y Método: Estudio observacional, seccional, con abordaje cuantitativo, realizado con 207 profesionales de la salud, médicos, enfermeros y técnicos de enfermería de un hospital en el estado de Minas Gerais, Brasil, de enero a noviembre de 2020. Los participantes fueron obtenidos a través de una muestra no probabilística y respondieron al cuestionario Hospital Survey on Patient Safety Culture, un instrumento ya validado para la realidad brasileña. Se utilizaron análisis estadísticos descriptivos y de regresión lineal múltiple; el nivel de significancia considerado fue de α =0,05. Resultados: La dimensión mejor evaluada fue "Aprendizaje organizacional - mejora continua" (64,4%). Ninguna dimensión se consideró un área fuerte por no recibir una puntuación ≥ 75%. Se consideraron áreas frágiles ocho dimensiones (≤ 50%), siendo la dimensión "Respuesta no punitiva al error" la peor evaluada (20,3%). El puntaje de seguridad del paciente otorgado por el profesional en su área laboral del hospital (β= 0,502, p <0,001) y el tiempo de trabajo laboral en el hospital (β= 0,135, p = 0,032) fueron estadísticamente significativos cuando se asociaron con la puntuación general. Conclusión: El estudio permitió identificar debilidades dentro de la institución, siendo la respuesta no punitiva a los errores la más preocupante. Los líderes deben proponer intervenciones que proporcionen un entorno libre de culpa para que los profesionales informen los eventos adversos. Considerar la seguridad del paciente como una prioridad de gestión puede aportar una mejor calidad a los servicios que ofrece la organización.
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Brazil has the second highest number of deaths due to COVID-19. Obesity has been associated with an important role in disease development and a worse prognosis. We aimed to explore epidemiological data from Brazil, discussing the potential relationships between obesity and COVID-19 severity in this country. We used a public database made available by the Ministry of Health of Brazil (182700 patients diagnosed with COVID-19). Descriptive statistics were used to characterize our database. Continuous data were expressed as median and analyzed by the nonparametric tests Mann-Whitney or one-sample Wilcoxon. The frequencies of categorical variables have been analyzed by chi-square tests of independence or goodness-of-fit. Among the number of deaths, 74% of patients were 60 years of age or older. Patients with obesity who died of COVID-19 were younger (59 years (IQR = 23)) than those without obesity (71 years (IQR = 20), P < 0.001, and η 2 = 0.0424). Women with obesity who died of COVID-19 were older than men (55 years (IQR = 25) vs. 50 (IQR = 22), P < 0.001, and η 2 = 0.0263). Furthermore, obesity increases the chances of needing intensive care unit (OR: 1.783, CI: 95%, and P < 0.001), needing ventilatory support (OR: 1.537, CI: 95%, and P < 0.001 and OR: 2.302, CI: 95%, and P < 0.001, for noninvasive and invasive, respectively), and death (OR: 1.411, CI: 95%, and P < 0.001) of patients hospitalized with COVID-19. Our analysis supports obesity as a significant risk factor for the development of more severe forms of COVID-19. The present study can direct a more effective prevention campaign and appropriate management of subjects with obesity.
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BACKGROUND: Surgical Tray Rationalization (STR) consists of a systematic reduction in the number of surgical instruments to perform specific procedures without compromising patient safety while reducing losses in the sterilization and assembly of trays. STR is one example of initiatives to improve process performance that have been widely reported in industrial settings but only recently have gained popularity in healthcare organizations. METHODS: We conduct a scoping review of the literature to identify and map available evidence on surgical tray management. Five methodological stages are implemented and reported; they are: identifying research questions, identifying relevant studies, study selection, charting the data, and collating, summarizing and reporting the results. RESULTS: We reviewed forty-eight articles on STR, which were grouped according to their main proposed approaches: expert analysis, lean practices, and mathematical programming. We identify the most frequently used techniques within each approach and point to their potential contributions to operational and economic dimensions of STR. We also consolidate our findings, proposing a roadmap to STR with four generic steps (prepare, rationalize, implement, and consolidate) and recommended associated techniques. CONCLUSIONS: To the best of our knowledge, ours is the first study that reviews and systematizes the existing literature on the subject of STR. Our study closes with the proposition of future research directions, which are presented as nine research questions associated with the four generic steps proposed in the STR roadmap.
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Racionalização , Instrumentos Cirúrgicos , Humanos , EsterilizaçãoRESUMO
In batch processing, process control is typically carried out comparing trajectories of process variables with those in an in-control set of batches that yielded products within specifications. However, one strong assumption of these schemes is that all batches have equal duration and are synchronized, which is often not satisfied in practice. To overcome that, dynamic time warping (DTW) methods may be used to synchronize stages and align the duration of batches. In this paper, three DTW methods are compared using supervised classification through the k-nearest neighbor technique to determine the in-control set in a milk chocolate conching process. Four variables were monitored over time and a set of 62 batches with durations between 495 and 1170 min was considered; 53% of the batches were known to be conforming based on lab test results and experts' evaluations. All three DTW methods were able to promote the alignment and synchronization of batches; however, the KMT method (Kassidas et al. in AIChE J 44(4):864-875, 1998) outperformed the others, presenting 93.7% accuracy, 97.2% sensitivity, and 90.3% specificity in batch classification as conforming and non-conforming. The drive current of the main motor was the most consistent variable from batch to batch, being deemed the most important to promote alignment and synchronization of the chocolate conching dataset.
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Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use.
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Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.
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Metaloendopeptidases/metabolismo , Animais , Comportamento Animal , Feminino , Masculino , Metaloendopeptidases/deficiência , Metaloendopeptidases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , FenótipoRESUMO
Studies suggest that the endocannabinoid and endovanilloid systems are implicated in the pathophysiology of schizophrenia. The Spontaneously Hypertensive Rats (SHR) strain displays impaired contextual fear conditioning (CFC) attenuated by antipsychotic drugs and worsened by pro-psychotic manipulations. Therefore, SHR strain is used to study emotional processing/associative learning impairments associated with schizophrenia and effects of potential antipsychotic drugs. Here, we evaluated the expression of CB1 and TRPV1 receptors in some brain regions related to the pathophysiology of schizophrenia. We also assessed the effects of drugs that act on the endocannabinoid/endovanilloid systems on the CFC task in SHRs and control animals (Wistar rats - WRs). The following drugs were used: AM404 (anandamide uptake/metabolism inhibitor), WIN55-212,2 (non-selective CB1 agonist), capsaicin (TRPV1 agonist), and capsazepine (TRPV1 antagonist). SHRs displayed increased CB1 expression in prelimbic cortex and cingulate cortex area 1 and in CA3 region of the dorsal hippocampus. Conversely, SHRs exhibited decreases in TRPV1 expression in prelimbic and CA1 region of dorsal hippocampus and increases in the basolateral amygdala. AM404, WIN 55,212-2 and capsaicin attenuated SHRs CFC deficit, although WIN 55,212-2 worsened SHRs CFC deficit in higher doses. WRs and SHRs CFC were modulated by distinct doses, suggesting that these strains display different responsiveness to cannabinoid and vanilloid drugs. Treatment with capsazepine did not modify CFC in either strains. The effects of AM404 on SHRs CFC deficit was not blocked by pretreatment with rimonabant (CB1 antagonist) or capsazepine. These results reinforce the involvement of the endocannabinoid/endovanilloid systems in the SHRs CFC deficit and point to these systems as targets to treat the emotional processing/cognitive symptoms of schizophrenia.
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Sintomas Afetivos/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Endocanabinoides/metabolismo , Esquizofrenia/metabolismo , Sintomas Afetivos/induzido quimicamente , Animais , Ácidos Araquidônicos/agonistas , Ácidos Araquidônicos/antagonistas & inibidores , Ácidos Araquidônicos/metabolismo , Ácidos Araquidônicos/farmacologia , Ácidos Araquidônicos/uso terapêutico , Agonistas de Receptores de Canabinoides/farmacologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Disfunção Cognitiva/induzido quimicamente , Endocanabinoides/agonistas , Endocanabinoides/antagonistas & inibidores , Masculino , Alcamidas Poli-Insaturadas/agonistas , Alcamidas Poli-Insaturadas/antagonistas & inibidores , Alcamidas Poli-Insaturadas/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Esquizofrenia/induzido quimicamente , Esquizofrenia/prevenção & controleRESUMO
The Spontaneously Hypertensive Rat (SHR) strain has been suggested as an animal model of schizophrenia, considering that adult SHRs display behavioral abnormalities that mimic the cognitive, psychotic and negative symptoms of the disease and are characteristic of its animal models. SHRs display: (I) deficits in fear conditioning and latent inhibition (modeling cognitive impairments), (II) deficit in prepulse inhibition of startle reflex (reflecting a deficit in sensorimotor gating, and associated with psychotic symptoms), (III) diminished social behavior (modeling negative symptoms) and (IV) hyperlocomotion (modeling the hyperactivity of the dopaminergic mesolimbic system/ psychotic symptoms). These behavioral abnormalities are reversed specifically by the administration of antipsychotic drugs. Here, we performed a behavioral characterization of young (27-50â¯days old) SHRs in order to investigate potential early behavioral abnormalities resembling the prodromal phase of schizophrenia. When compared to Wistar rats, young SHRs did not display hyperlocomotion or PPI deficit, but exhibited diminished social interaction and impaired fear conditioning and latent inhibition. These findings are in accordance with the clinical course of schizophrenia: manifestation of social and cognitive impairments and absence of full-blown psychotic symptoms in the prodromal phase. The present data reinforce the SHR strain as a model of schizophrenia, expanding its validity to the prodromal phase of the disorder.
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Modelos Animais de Doenças , Sintomas Prodrômicos , Ratos Endogâmicos SHR , Esquizofrenia , Animais , Antipsicóticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Masculino , Atividade Motora , Inibição Pré-Pulso/efeitos dos fármacos , Ratos Wistar , Reflexo de Sobressalto/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologiaRESUMO
Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.
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Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1-/-) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1-/- exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1-/- and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1-/- mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1-/- mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1-/- mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation.
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Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD - a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs' hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.
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Movement disorders such as Parkinson's disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field.
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Questionnaires that assess symptoms of schizophrenia patients undergo strict statistical validation, often using confirmatory factor analysis (CFA). CFA allows testing the existence of a trait that both collectively explains the symptoms and gathers the information in a single general index. In rodents, some behaviors are used to model psychiatric symptoms, but no single test or paradigm adequately captures the disorder's phenotype in toto. This work investigated the existence of a behavioral trait in the SHR strain underlying five behavioral tasks used in schizophrenia animal studies and altered in this strain: locomotor activity, rearing behavior, social interaction, prepulse inhibition of startle and contextual fear conditioning. The analysis was conducted on a sample of Wistar (nâ¯=â¯290) and Spontaneously Hypertensive Rats (SHRs, nâ¯=â¯290). CFA showed the existence of a continuous trait in both strains, and higher values among SHRs. This work is the first to demonstrate the existence of a schizophrenia-like trait in an animal model. We suggest that using CFA to evaluate behavioral parameters in animals might facilitate the pre-clinical investigation of psychiatric disorders, diminishing the gap between animal and human studies.
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Modelos Animais de Doenças , Ratos Endogâmicos SHR , Psicologia do Esquizofrênico , Animais , Comportamento Animal , Simulação por Computador , Condicionamento Psicológico , Análise Fatorial , Medo , Masculino , Método de Monte Carlo , Atividade Motora , Inibição Pré-Pulso , Ratos Wistar , Reflexo de Sobressalto , Comportamento SocialRESUMO
AIMS: The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. METHODS: Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. RESULTS: Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. CONCLUSION: Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia.
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Transtornos Mentais/etiologia , Transtornos Mentais/prevenção & controle , Doadores de Óxido Nítrico/uso terapêutico , Nitroprussiato/uso terapêutico , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fatores Etários , Animais , Peso Corporal/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medo/efeitos dos fármacos , Relações Interpessoais , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2-5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals' performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements - but not the decrease in locomotion - induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson's disease and tardive dyskinesia.
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Schizophrenia is a severe psychiatric disorder that involves positive, negative and cognitive symptoms. Prepulse inhibition of startle reflex (PPI) is a paradigm that assesses the sensorimotor gating functioning and is impaired in schizophrenia patients as well as in animal models of this disorder. Recent data point to the participation of the endocannabinoid system in the pathophysiology and pharmacotherapy of schizophrenia. Here, we focus on the effects of cannabinoid drugs on the PPI deficit of animal models of schizophrenia, with greater focus on the SHR (Spontaneously Hypertensive Rats) strain, and on the future prospects resulting from these findings.
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Schizophrenia is a highly disabling mental disorder, in which genetics and environmental factors interact culminating in the disease. The treatment of negative symptoms and cognitive deficits with antipsychotics is currently inefficient and is an important field of research. Environmental enrichment (EE) has been suggested to improve some cognitive deficits in animal models of various psychiatric disorders. In this study, we aimed to evaluate a possible beneficial effect of early and long-term exposure to EE on an animal model of schizophrenia, the SHR strain. Young male Wistar rats (control strain) and SHRs (21 post-natal days) were housed for 6weeks in two different conditions: in large cages (10 animals per cage) containing objects of different textures, forms, colors and materials that were changed 3 times/week (EE condition) or in standard cages (5 animals per cage - Control condition). Behavioral evaluations - social interaction (SI), locomotion, prepulse inhibition of startle (PPI) and spontaneous alternation (SA) - were performed 6weeks after the end of EE. SHRs presented deficits in PPI (a sensorimotor impairment), SI (mimicking the negative symptoms) and SA (a working memory deficit), and also hyperlocomotion (modeling the positive symptoms). EE was able to reduce locomotion and increase PPI in both strains, and to prevent the working memory deficit in SHRs. EE also increased the number of neurons in the CA1 and CA3 of the hippocampus. In conclusion, EE can be a potential nonpharmacological strategy to prevent some behavioral deficits associated with schizophrenia.