Solvent-free MALI-MGRE Procedure for Synthesizing 1,4-thiazolidin-4- one MALI (Mercaptoacetic Acid Looking Imine) MGRE (Mechanical Grinding Reaction Equipment).

BACKGROUND: 1,3-Thiazolidin-4-ones are heterocycles whose importance in the pharmaceutical market has already been established. Many of these synthetic derivatives, which contain a thiazolidinone nucleus, are currently used in various commercial formulations or are already in clinical trials for the treatment of disease for their anticonvulsant, antihypertensive and antidiabetic activities in addition to their activity against Streptomyces. 1,3-Thiazolidin-4-ones are produced mainly by cyclo condensation between an imine (generated in situ by the reaction of an aldehyde with an amine) and α-mercaptoacetic acid, known as the MALI (Mercaptoacetic Acid Looking Imine) reaction. OBJECTIVE: A solvent-free methodology was developed to synthesize a 1,3-thiazolidin-4-one family by the MALI reaction. An apparatus was developed to grind a solid-liquid mixture of anilines, benzaldehydes and thioglycolic acid to activate the reaction. This apparatus was named MGRE (mechanical grinding reaction equipment). METHODS: Substituted aniline 2 (4 mmol), substituted benzaldehyde 1 (4 mmol) and thioglycolic acid 3 (12 mmol) were placed in a mortar. The reagents were macerated using the MGRE at room temperature for a specified time period. At the end of the reaction, the product was poured into ice, the precipitate formed was neutralized (with 5% NaHCO3), and the solution was extracted in ethyl acetate and dried in MgSO4. The solid was recrystallized from MeOH/H2O. RESULTS: The developed MGRE is a modification of a rod used in a mechanical stirrer. This adaptation is inexpensive and simple in construction, and it enables reactions to occur over long periods of time that would be exhaustive for manual grinding. Fifteen (1,3) thiazolidin-4-ones were produced. The products were synthesized using the solvent-free MALI-MGRE procedure. CONCLUSIONS: The MALI-MGRE methodology developed to produce 1,3-thiazolidin-4-ones showed a good reaction scope, has an easy work-up and is solvent-free. Consequently, MALI-MGRE is classified as a green methodology. An innovation of this study is the construction of the MGRE, which involves modifying the rod in a mechanical stirrer. The equipment is easy and inexpensive to construct and may be useful for various reactions involving grinding.

Avanços e perspectivas no diagnóstico molecular da leucemia mieloide aguda: revisão sistemática / Advances and perspectives in the molecular diagnosis of acute myeloid leukemia: systematic review

O câncer do colo do útero é o quarto tumor mais comum entre mulheres no mundo e o terceiro no Brasil. A detecção precoce e a identificação das lesões cervicais são essenciais no rastreamento do câncer cervical. Nos últimos anos, vários marcadores têm sido apresentados como possíveis candidatos para a triagem eficiente de exames citológicos com anormalidades das células epiteliais. O objetivo deste trabalho é analisar a correlação com a expressão imuno-histoquimica dos biomarcadores p16 e Ki-67 com lesão intraepitelial cervical de alto grau na detecção molecular DNA/HPV de alto risco. A metodologia de pesquisa empregada é uma revisão sistemática, realizada por meio de buscas nas bases de dados eletrônica Literatura Latino-Americana em Ciência e Saúde (LILACS), Scientific Electronic Library Online (SCIELO), National Library of Medicine (MEDLINE) de artigos publicados no período de 2005 a 2019 nos idiomas português, inglês e espanhol. Concluiu-se que o uso das proteínas p16 e Ki67 auxilia na identificação das mudanças que acontecem durante a progressão da lesão cervical, aprimorando os métodos de rastreio atuais. O gene p53, a pRb e ciclinas também têm um papel crítico na carcinogênese e, desta maneira, também têm sido indicados para entrar nos painéis de estudo.

Introduction: Acute myeloid leukemia (AML) is a genetically heterogeneous malignant clonal disorder of the hematopoietic system, characterized by the uncontrolled proliferation of abnormal and immature blast cells and impaired production of normal blood cells. Objective: to present the advances in diagnosis in Acute Myeloid Leukemia through the techniques of molecular biology. Methodology: The research was carried out in the electronic databases for scientific articles of the search portal PubMed, NCBI, BVSMS, also SciELO. Results: Molecular techniques, including real-time quantitative PCR (RT-qPCR), digital PCR and technologies based on new generation sequencing, can be standardized and used to detect AML-associated gene changes. Conclusion: The advance in molecular diagnosis can be promising in the ideal and personalized treatment.

The impact of physical functions on depressive symptoms in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. The impact of MS transcends physical functions and extends to psychological impairment. Approximately 50% of people with MS develop depressive symptoms during their lifetime and depressive symptoms may predict impairment of physical functions. However, prediction of depressive symptoms based on objective measures of physical functions is still necessary. OBJECTIVE: To compare physical functions between people with MS presenting depressive symptoms or not and to identify predictors of depressive symptoms using objective measures of physical functions. METHODS: Cross-sectional study including 26 people with MS. Anxiety and/or depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and by the Hospital Anxiety and Depression Scale (HADS). Outcomes of physical functions included: the Nnnine-hole Ppeg Ttest (NHPT), knee muscle strength, balance control, the Timed Up and Go Test (TUG), and the 6-minute walk test (6MWT). Perceived exertion was measured using the Borg scale. RESULTS: The frequency of depressive symptoms was 42% in people with MS. Balance control during a more challenging task was impaired in people with MS who presented depressive symptoms. Balance could explain 21-24% of the variance in depressive symptoms. 6MWT and TUG presented a trend of significance explaining 16% of the variance in the BDI-II score. CONCLUSIONS: Impairment in physical functions consists in a potential predictor of depressive symptoms in people with MS. Exercise interventions aiming at the improvement of physical functions, together with the treatment of depressive symptoms and conventional medical treatment, are suggested.

The impact of physical functions on depressive symptoms in people with multiple sclerosis / O impacto das funções físicas nos sintomas depressivos em pessoas com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. The impact of MS transcends physical functions and extends to psychological impairment. Approximately 50% of people with MS develop depressive symptoms during their lifetime and depressive symptoms may predict impairment of physical functions. However, prediction of depressive symptoms based on objective measures of physical functions is still necessary. Objective: To compare physical functions between people with MS presenting depressive symptoms or not and to identify predictors of depressive symptoms using objective measures of physical functions. Methods: Cross-sectional study including 26 people with MS. Anxiety and/or depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and by the Hospital Anxiety and Depression Scale (HADS). Outcomes of physical functions included: the Nnnine-hole Ppeg Ttest (NHPT), knee muscle strength, balance control, the Timed Up and Go Test (TUG), and the 6-minute walk test (6MWT). Perceived exertion was measured using the Borg scale. Results: The frequency of depressive symptoms was 42% in people with MS. Balance control during a more challenging task was impaired in people with MS who presented depressive symptoms. Balance could explain 21-24% of the variance in depressive symptoms. 6MWT and TUG presented a trend of significance explaining 16% of the variance in the BDI-II score. Conclusions: Impairment in physical functions consists in a potential predictor of depressive symptoms in people with MS. Exercise interventions aiming at the improvement of physical functions, together with the treatment of depressive symptoms and conventional medical treatment, are suggested.

RESUMO Introdução: A esclerose múltipla (EM) é uma doença imunomediada que afeta o sistema nervoso central. O impacto da doença transcende as funções físicas e se estende a comprometimento psicológico. Aproximadamente 50% das pessoas com EM desenvolvem sintomas depressivos e estes podem predizer o comprometimento das funções físicas. No entanto, a previsão de sintomas depressivos com base em medidas objetivas das funções físicas ainda é necessária. Objetivos: Comparar funções físicas entre pessoas com EM que apresentam ou não sintomas depressivos e identificar preditores de sintomas depressivos usando medidas objetivas de funções físicas. Métodos: Estudo transversal incluindo 26 pessoas com EM. A ansiedade e/ou sintomas depressivos foram avaliadas pelo Inventário de Depressão de Beck-II (Beck Depression Inventory - BDI-II) e pela Escala Hospitalar de Ansiedade e Depressão. Os resultados das funções físicas incluíram: teste de PEG de nove buracos, força muscular do joelho, controle de equilíbrio, teste Timed Up and Go (TUG) e teste da caminhada de seis minutos (TC6M). A fadiga percebida foi medida usando a escala de Borg. Resultados: A frequência de sintomas depressivos na amostra foi de 42%. O controle do equilíbrio durante tarefa desafiadora foi prejudicado em pessoas com EM e sintomas depressivos. O equilíbrio pode explicar 21-24% da variação nos sintomas depressivos. O TC6M e o TUG apresentaram tendência de significância que explica 16% da variância no escore do BDI-II. Conclusões: O comprometimento das funções físicas é potencial preditor de sintomas depressivos em pessoas com EM. São sugeridas intervenções de exercícios físicos visando melhora das funções físicas, juntamente com o tratamento médico convencional e dos sintomas depressivos.

Relationship between depression, alcohol and / or tobacco abuse of those responsible and children's oral health

Objective :To investigate the influence of parental depression and smoking and alcohol use by parents/caregivers use on oral health in children aged 5-11 years of both sexes. Methods: A cross-sectional study was conducted involving 85 children and their parents/caregivers. Adult respondents completed three questionnaires to assess depression and alcohol and tobacco use: two versions of the PHQ (PatientHealth Questionnaire; PHQ-2 and PHQ-9), AUDIT (Alcohol Use DisordersIdentification Test) for risk assessment of alcohol dependence and abuse, and the Fagerström Test for Nicotine Dependence (FTND). The PHQ-2 contained two questions requiring an affirmative or negative answer. Children underwent oral examinations to evaluate biofilm control, gingival bleeding and caries index, specifically DMFT index. Relationships among variables were evaluated using chi-squared tests and Fisher's exact test. Results: Only 10.6% of parents and caregivers consumed tobacco and 24,7% of parents or caregivers manifested depressive symptoms. Regarding alcohol consumption, 10.6% of caregivers presented risk consumption or dependence. A positive association was found between children'sgingival bleeding and their caregivers' risk of alcohol dependence (p=0.038). Conclusion: A positive association between caregivers' risk of alcohol dependence and the presence of gingival bleeding in children was found. Caregivers' depression and alcohol and tobacco use did not influence children's caries.

Objetivo: Investigar a influência da depressão parental e do uso de cigarro e álcool pelos pelos pais/cuidadores na saúde bucal de crianças de 5 a 11 anos de ambos os sexos. Métodos: Um estudo do tipo transversal foi conduzido com 85 crianças e seus respectivos cuidadores. Para detectar a presença de depressão, duas versões do PHQ (Pacient Health Questionnaire) foram aplicadas: o PHQ-2, contendo duas perguntas com opção de resposta afirmativa ou negativa e o segundo, PHQ-9. Para o uso de álcool foi aplicado o AUDIT (Alcohol Use Disorders Identification Test) para avaliação do risco de dependência e abuso de álcool; e o Fagerstrom para dependência de nicotina. As crianças foram submetidas a exames orais para avaliação do controle de biofilme, sangramento gengival e presença de cárie (índices CPO-D e ceo-d). Para verificar a associação entre as diferentes variáveis, foram utilizados os testes Qui-quadrado e Exato de Fisher. Resultados: Somente 10,6% dos responsáveis faziam uso de tabaco e 24,7% dos mesmos apresentavam sintomas de depressão. Em relação ao consumo de álcool, 10,6% apresentavam consumo de risco ou dependência. Verificou-se associação entre sangramento gengival nas crianças e o risco de dependência de álcool dos responsáveis (p=0,038). Conclusão: Concluiu-se que há uma associação positiva entre o risco de dependência de álcool dos responsáveis e a presença de sangramento gengival no paciente e que a depressão, o uso de álcool e de tabaco pelos cuidadores não influência na experiência de cárie das crianças.

Eco-friendly and Enantiospecific Biginelli Synthesis Using (+)-Myrtenal as the Substrate - An Impeccable and Unequivocal Analysis of the Product.

BACKGROUND: We found in the literature, an excellent review of the Biginelli reaction that addresses the methodologies for obtaining enantiopure dihydropyrimidinones (DHPMs). In 1992, optically pure DHPMs were obtained by fractional crystallization of the diastereomeric ammonium salt derivative with (S)-(-) and (R)- (+)-α-methyl benzylamine and by other chiral resolution techniques, such as chiral high-performance liquid chromatography (HPLC). Asymmetric syntheses of these compounds are also explained in the literature. The main strategy is to use acid catalysts such as organophosphates, organometallic complexes, amines and diamines, nanocomposites, and chiral ionic liquids, e.g., L-prolinium sulfate (Pro2SO4). OBJECTIVE: The objective was to study the Biginelli reaction with a chiral aldehyde. METHODS: A mixture of ethyl acetoacetate (0.26 g, 3 mmol), urea (0.18 g, 3 mmol) and ethyl lactate (EL) (1 mL) was left under heating at 70°C and stirring for 1 h. Next, (-)-(1R)-myrtenal (0.45 g, 3 mmol) was added, and the medium was heated for 5 h more until the formation of a white solid. Ten millilitres of distilled water was added, and the product was extracted with CH2Cl2 (3 x 4 mL). The solvent was evaporated, and the product was recrystallized from ethanol-water. RESULTS AND DISCUSSION: (+)-Myrtenal was used as a chiral substrate for a study that led to ethyl (R)-4-((1R,5S)- 6,6-dimethylbicyclo [3.1.1]hept-2-en-2-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate by the Biginelli synthesis using EL as a green solvent. The result is the first example of the enantiospecific Biginelli reaction. The product was exhaustively characterized by several physical analysis methods, i.e., 1H, 13C and 2D nuclear magnetic resonance (NMR) spectroscopies, infrared (IR) spectroscopy, mass spectrometry (MS), and high-resolution MS (HRMS), and its structure was unequivocally elucidated by X-ray crystallography. CONCLUSION: Compound (4R)-4-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-6-methyl-2-oxo-1,2,3,4- tetrahydropyrimidine- 5-ethyl carboxylate is the first example of the enantiospecific Biginelli reaction. In addition, the process has the advantage of using EL as a green solvent. The product was characterized by 1H, 13C, and 2D NMR and IR spectroscopy, MS, HRMS, and X-ray crystallography.

FRENECTOMIA LINGUAL COM USO DO LASER DE ALTA POTÊNCIA EM ODONTOPEDIATRIA: RELATO DE CASO / LINGUAL FRENECTOMY WITH HIGH-POWER LASER IN PEDIATRIC PATIENTS: CASE REPORT

A anquiloglossia, conhecida também como língua presa, representa uma anomalia do desenvolvimento caracterizada por alteração no freio da língua que resulta em limitações dos movimentos da mesma. O tratamento desta patologia pode ser através da frenotomia ou da frenectomia, que são diferenciadas de acordo com sua extensão. Com isso, o presente relato tem por finalidade demonstrar o caso clínico de frenectomia lingual usando laser de alta potência, demonstrando seus benefícios e apresentando os resultados satisfatórios obtidos. O caso apresentado refere-se a paciente pediátrico, de um ano de idade, que compareceu à Clínica do Curso de Especialização em Odontopediatria do Instituto de Odontologia Multidisciplinar (IOM) com seu responsável legal (mãe), com indicação para frenectomia lingual. Utilizou-se o laser de alta potência (de diodo) para a realização da cirurgia. Diversas vantagens são observadas com o uso do laser cirúrgico de alta potência, dentre elas, menor tempo cirúrgico, campo operatório mais limpo, hemostasia, redução da dor e infecção pós- operatória, menor contração tecidual, ausência de sutura, redução do trauma, edema e otimização da cicatrização.

Ankyloglossia, also known as a prey tongue, represents a developmental anomaly characterized by a change in the tongue's braking resulting in limitations of tongue movements. The treatment of this pathology can be through the frenotomy or the frenectomy, which are differentiated according to its extension. Therefore, this report aims to demonstrate the report of clinical case of lingual frenectomy with high-power laser, demonstrating its benefits and presenting the satisfactory results obtained. The case presented refer to pediatric patient, one year old, who attended the Clinic of the Specialization Course in Pediatric Dentistry of the Institute of Multidisciplinary Dentistry with their legal guardian (mother), with indication for lingual frenectomy. The high-power laser (of diode) was used for the accomplishment of the surgery. The advantages of high-power surgical laser, such as shorter surgical time, cleaner operative field, hemostasis, reduction of pain and postoperative infection, less tissue contraction, absence of suture, reduction of trauma, edema and optimization of healing.

Decisions about deep brain stimulation therapy in Parkinson's disease.

Parkinson's disease can be treated surgically in patients who present with motor complications such as fluctuations and dyskinesias, or medically-refractory disabling tremor. In this review, a group of specialists formulated suggestions for a preoperative evaluation protocol after reviewing the literature published up to October 2017. In this protocol, eligibility and ineligibility criteria for surgical treatment were suggested, as well as procedures that should be carried out before the multidisciplinary therapeutic decisions. The review emphasizes the need to establish "DBS teams", with professionals dedicated specifically to this area. Finally, surgical target selection (subthalamic nucleus or globus pallidus internus) is discussed briefly, weighing the pros and cons of each target.

Suicidal ideation, anxiety, and depression in patients with multiple sclerosis.

INTRODUCTION: Psychiatric disorders frequently occur in patients with multiple sclerosis (MS); however, limited reports are available on these comorbidities. We aimed to investigate the relationships among MS, anxiety, depression, and suicidal ideation. METHODS: One hundred and thirty two patients with relapsing-remitting MS were evaluated using the Expanded Disability Status Scale, Beck Depression Inventory-II (BDI-II), Beck Scale for Suicide Ideation (BSI), and Hospital Anxiety and Depression Scale. RESULTS: A hierarchical regression analysis was performed to evaluate the variables. The regression equation significantly predicted the BSI score (R2 = 0.306; adjusted R2 = 0.273; F (9, 125) = 9.18; p < 0.0005), and the BDI-II score was the only variable that contributed significantly to this model (p < 0.0005). CONCLUSIONS: A high prevalence of depression and anxiety, and a higher rate of suicidal ideation were identified in MS patients compared to the general population. The presence of depressive symptoms appeared to have a direct influence on the risk of suicide.

Decisions about deep brain stimulation therapy in Parkinson's disease / Decisões a respeito da terapia com estimulação cerebral profunda na doença de Parkinson

ABSTRACT Parkinson's disease can be treated surgically in patients who present with motor complications such as fluctuations and dyskinesias, or medically-refractory disabling tremor. In this review, a group of specialists formulated suggestions for a preoperative evaluation protocol after reviewing the literature published up to October 2017. In this protocol, eligibility and ineligibility criteria for surgical treatment were suggested, as well as procedures that should be carried out before the multidisciplinary therapeutic decisions. The review emphasizes the need to establish "DBS teams", with professionals dedicated specifically to this area. Finally, surgical target selection (subthalamic nucleus or globus pallidus internus) is discussed briefly, weighing the pros and cons of each target.

RESUMO A doença de Parkinson pode ser tratada cirurgicamente em pacientes que desenvolveram complicações motoras, como flutuações e discinesias, ou tremores refratários ao uso de medicação. Nesta revisão, um grupo de especialistas formulou sugestões para um protocolo de avaliação pré-operatória, depois de revisar a literatura publicada até outubro de 2017. Neste protocolo, são sugeridos critérios de elegibilidade e inadmissibilidade para tratamento cirúrgico, bem como procedimentos que devem ser realizados antes das decisões terapêuticas multidisciplinares. A revisão enfatiza a necessidade de estabelecer "equipes de DBS", com profissionais dedicados especialmente a esta área. Ao final, a seleção do alvo cirúrgico (núcleo subtalâmico ou globo pálido interno) é discutida brevemente, ponderando prós e contras de cada escolha.

Suicidal ideation, anxiety, and depression in patients with multiple sclerosis / Ideação suicida, ansiedade e depressão em pacientes com esclerose múltipla

ABSTRACT Psychiatric disorders frequently occur in patients with multiple sclerosis (MS); however, limited reports are available on these comorbidities. We aimed to investigate the relationships among MS, anxiety, depression, and suicidal ideation. Methods: One hundred and thirty two patients with relapsing-remitting MS were evaluated using the Expanded Disability Status Scale, Beck Depression Inventory-II (BDI-II), Beck Scale for Suicide Ideation (BSI), and Hospital Anxiety and Depression Scale. Results: A hierarchical regression analysis was performed to evaluate the variables. The regression equation significantly predicted the BSI score (R2 = 0.306; adjusted R2 = 0.273; F (9, 125) = 9.18; p < 0.0005), and the BDI-II score was the only variable that contributed significantly to this model (p < 0.0005). Conclusions: A high prevalence of depression and anxiety, and a higher rate of suicidal ideation were identified in MS patients compared to the general population. The presence of depressive symptoms appeared to have a direct influence on the risk of suicide.

RESUMO Transtornos psiquiátricos frequentemente ocorrem em pacientes com esclerose múltipla (EM). No entanto, os artigos sobre estas comorbidades são limitados. Pretendemos investigar as relações entre EM, ansiedade, depressão e ideação suicida. Métodos: Cento e trinta e dois pacientes com EM remitente-recorrente foram avaliados usando a Escala de Estado de Incapacidade Expandida, Inventário de Depressão de Beck-II (IDB-II), Escala de Beck para Ideação de Suicídio (BSI) e Escala de Ansiedade e Depressão. Resultados: Uma análise de regressão hierárquica foi realizada para avaliar as variáveis. A equação de regressão previu significativamente o escore BSI (R2 = 0,306; R2 ajustado = 0,273; F (9,125) = 9,18; p < 0,0005) e o escore no IDB-II foi a única variável que contribuiu significativamente para este modelo (p < 0,0005). Conclusões: Uma alta prevalência de depressão e ansiedade e uma maior taxa de ideação suicida foram identificadas em pacientes com EM em comparação com a população em geral. A presença de sintomas depressivos pareceu ter uma influência direta no risco de suicídio.

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado / Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado / Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.(AU)

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.(AU)