Phytohormone abscisic acid boosts pentobarbital-induced sleep through activation of GABA-A, PPARß and PPARγ receptor signaling / O fito-hormônio ácido abscísico estimula o sono induzido por fenobarbital por meio de ativação da sinalização de receptores GABA-A, PPARß e PPARγ

ABSTRACT Background: Sleep disorders induce anxiety and forgetfulness and change habits. The chemical hypnotic drugs currently used have serious side effects and, therefore, people are drawn towards using natural compounds such as plant-based healing agents. Abscisic acid (ABA) is produced in a variety of mammalian tissues and it is involved in many neurophysiological functions. Objective: To investigate the possible effect of ABA on pentobarbital-induced sleep and its possible signaling through GABA-A and PPAR (γ and β) receptors, in male Wistar rats. Methods: The possible effect of ABA (5 and 10 µg/rat, intracerebroventricularly) on sleep onset latency time and duration was evaluated in a V-maze model of sleep. Pentobarbital sodium (40 mg/kg, intraperitoneally) was injected to induce sleep 30 min after administration of ABA. PPARβ (GSK0660, 80 nM/rat), PPARγ (GW9662, 3 nM/rat) or GABA-A receptor (bicuculline, 6 µg/rat) antagonists were given 15 min before ABA injection. Diazepam (2 mg/kg, intraperitoneally) was used as a positive control group. Results: ABA at 5 µg significantly boosted the pentobarbital-induced subhypnotic effects and promoted induction of sleep onset in a manner comparable to diazepam treatment. Furthermore, pretreatment with bicuculline significantly abolished the ABA effects on sleep parameters, while the amplifying effects of ABA on the induction of sleep onset was not significantly affected by PPARβ or PPARγ antagonists. The sleep prolonging effect of ABA was significantly prevented by both PPAR antagonists. Conclusions: The data showed that ABA boosts pentobarbital-induced sleep and that GABA-A, PPARβ and PPARγ receptors are, at least in part, involved in ABA signaling.

RESUMO Introdução: Os distúrbios do sono induzem a ansiedade e esquecimento e mudam hábitos. Os medicamentos hipnóticos químicos utilizados atualmente têm efeitos colaterais graves e, portanto, as pessoas são atraídas para o uso de compostos naturais, como agentes de cura à base de plantas. O ácido abscísico (ABA) é produzido em uma variedade de tecidos de mamíferos e está envolvido em muitas funções neurofisiológicas. Objetivo: Investigar o possível efeito do ABA no sono induzido por pentobarbital e sua possível sinalização por meio dos receptores GABA-A e PPAR (γ e β), em ratos Wistar machos. Métodos: O possível efeito do ABA (5 e 10 µg/rato, intracerebroventricularmente) no tempo de latência e duração do início do sono foi avaliado em um modelo de labirinto em V de sono. Pentobarbital sódico (40 mg/kg, intraperitonealmente) foi injetado para induzir o sono 30 minutos após a administração de ABA. PPARβ (GSK0660, 80 nM/rato), PPARγ (GW9662, 3 nM/rato) ou antagonistas do receptor GABA-A (bicuculina, 6 µg/rato) foram administrados 15 minutos antes da injeção de ABA. Diazepam (2 mg/kg, intraperitonealmente) foi utilizado como grupo de controle positivo. Resultados: ABA a 5 µg aumentou significativamente os efeitos sub-hipnóticos induzidos por pentobarbital e promoveu a indução do início do sono de forma comparável ao tratamento com diazepam. Além disso, o pré-tratamento com bicuculina aboliu significativamente os efeitos do ABA nos parâmetros do sono, ao passo que os efeitos amplificadores do ABA na indução do início do sono não foram significativamente afetados pelos antagonistas do PPARβ ou PPARγ. O efeito de prolongamento do sono do ABA foi significativamente prevenido por ambos os antagonistas do PPAR. Conclusões: Os dados mostraram que o ABA estimula o sono induzido por pentobarbital e que os receptores GABA-A, PPARβ e PPARγ estão, pelo menos em parte, envolvidos na sinalização ABA.

A prescrição de benzodiazepínicos no Brasil: uma análise da literatura / The prescription of benzodiazepines in Brazil: a literature review

Benzodiazepínicos são medicamentos psicotrópicos de prescrição restrita e sujeitos a controle especial, conforme a Portaria nº 344, de 12 de maio de 1998. São utilizados como hipnóticos e sedativos, sendo bastante comuns na prática clínica. O uso prolongado destes fármacos pode causar dependência e por isso é necessário identificar seu perfil de prescrição. Este estudo busca revisar a literatura sobre os trabalhos que descreveram o uso de benzodiazepínicos no Brasil. Para isso, uma busca direta foi realizada em três bases de dados, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), PubMed e Scientific Eletronic Library Online (SciELO), utilizando os descritores prescrição/prescription, benzodiazepínicos/benzodiazepines, Brasil/Brazil. Depois de aplicados os critérios de inclusão e exclusão, restaram 12 artigos, os quais foram analisados. A análise destes trabalhos mostrou que, no Brasil, os benzodiazepínicos são utilizados especialmente por mulheres com tendência ao aumento do uso com o avançar da idade. Desta maneira, conclui-se que permanece a necessidade de políticas públicas que busquem o uso racional destes fármacos.

Benzodiazepines are prescription restricted psychotropic drugs, subject to special control according to Decree nº 344 of May 12, 1998. They are used as hypnotics and sedatives, being widely used in clinical practice. Prolonged use of these drugs can cause dependence, and therefore it is necessary to identify their prescription profile. This study aims to review the literature on studies that described the use of benzodiazepines in Brazil. For such, a direct search was conducted in databases, such as LILACS, Pubmed and SciELO, with the descriptors, in Portuguese and English, "prescrição" (prescription), "benzodiazepínicos" (benzodiazepines) and "Brasil" (Brazil). After applying the criteria for inclusion and exclusion, 12 articles remained, which were analyzed in this work. The analysis of these data has shown that, in Brazil, benzodiazepines are used especially by women with a tendency to increased use with advancing age. On this wat, we might conclude that Brazil's needs to improve his politics to promote rational use of Benzodiazepines.

Identification of types of GABAA receptors in neurons in brain tissues at target of anesthetic action of isoflurane in mice / 中华麻醉学杂志

Objective To identify the types of γ?aminobutyric acid type A ( GABAA ) receptors in neurons in brain tissues at the target of anesthetic action of isoflurane in mice. Methods Two mouse strains were developed that were either sensitive or resistant to isoflurane. One hundred isoflurane?sensitive ICR∕CD?1 mice ( 50 males, 50 females) and 100 isoflurane?resistant ICR∕CD?1 mice ( 50 males, 50 fe?males) , aged 65-70 days, were used in this study. Brain tissues were obtained, and total RNA was ex?tracted and then reverse transcribed to cDNA using AMV reverse transcriptase. Polymerase chain reaction was used to detect the cDNA sequences. Chi?square analysis was used to compare the cDNA sequence of each GABAA receptor subunit between two strains. Results The cDNA sequence of GABAA receptor sub?units α1?6 , β2,3 andγ1?3 in isoflurane?sensitive strain was completely consistent with that in isoflurane?resist?ant strain. A single nucleotide polymorphism at the nucleotide position 462 ( C∕G) in the β1 sequence was found. The allele C frequencies were 11.0% and 87.0% in isoflurane?sensitive strain and isoflurane?resistant strain, respectively. Compared with isoflurane?sensitive strain, the allele C frequency in cDNA sequences of β1 subunit was significantly increased in isoflurane?resistant strain ( P<0.01) . Conclusion β1 subunit?containing GABAA receptor in neurons in brain tissues is the target of anesthetic action of isoflurane in mice.

Utilização de benzodiazepínicos e estratégias farmacêuticas em saúde mental / Use of benzodiazepines and drug strategies in mental health

O artigo enfoca a heterogeneidade no uso de benzodiazepínicos, sob o enfoque farmacêutico, observada nos Centros de Atenção Psicossocial e Unidades Básicas de Saúde da Família. Os benzodiazepínicos estão incluídos entre os medicamentos mais prescritos para tratar distúrbios de ansiedade. Os avanços da reforma psiquiátrica, a criação dos Centros de Atenção Psicossocial (Caps) e o redirecionamento das atividades de saúde primária tornam imperiosa a adequação da prática farmacêutica através de atividades de orientação e acolhimento ao usuário de benzodiazepínicos.

This article focuses on the discrepancies in the use of benzodiazepines, under the pharmaceutical approach, observed daily in Centers of Psychosocial Care (Caps) and in Basic Units of Family Health. Benzodiazepines are among the most prescribed medications for the treatment of anxiety disorders. Advances in psychiatric reform, the creation of Caps and the new approach to primary health activities make imperative the adequacy of pharmaceutical practice through guidance and care activities to benzodiazepines' users.

Benzodiazepine use among employees of a private company / Consumo de benzodiazepinas en trabajadores de una empresa privada / Consumo de benzodiazepinas por trabalhadores de uma empresa privada

This study aimed to identify variables associated to the consumption of benzodiazepine among workers of a private company in the VIII Region, Chile. This is a cross-sectional and correlative study. Study population: 40 employees of a private company. The instruments included a questionnaire on socio-demographic variables and a benzodiazepine questionnaire. There was no record of benzodiazepine consumption at the moment of the study. Twenty percent (20 percent) of the interviewees had already used benzodiazepine in the past, whereas, half of them (10 percent) in the last year. The bivariate analysis of the last year consumption of benzodiazepine with work hours variables showed no significant relation (p=0.073). No association was found between benzodiazepine consumption and socio-demographic variables among the study participants.

El propósito de este estudio fue identificar las variables asociadas al consumo de benzodiazepinas en población trabajadora de una institución privada de la VIII Región, Chile. Diseño cuantitativo, transversal y correlacional. Población del estudio: 40 trabajadores de una empresa privada de la VIII Región, Chile. Instrumentos recolectores de datos. Cuestionario de variables biosociodemográficas y Cuestionario de benzodiazepinas. No se registró consumo de benzodiazepinas al momento del estudio. 20 por ciento de los entrevistados tenía antecedentes de consumo de benzodiazepinas en el pasado, de ellos la mitad (10 por ciento) en el último año. El análisis bivariado del consumo de benzodiazepinas en el último año con variables del trabajo sólo mostró una relación débilmente significativa (p= 0,073) con la jornada de trabajo. No se encontró asociación entre el consumo de benzodiazepines y las variables sociodemográficas entre los participantes del estudio.

O propósito deste estudo foi avaliar as variáveis associadas ao consumo de benzodiazepínicos em população trabalhadora de uma instituição privada da VIII Região, Chile. Este é um estudo quantitativo, transversal e correlacional. Participaram do estudo 40 trabalhadores de uma empresa privada da VIII Região, Chile. Para coleta dos dados utilizou-se um questionário com informações relacionadas às variáveis sócio-demográficas e Questionário de benzodiazepínicos. Não foi identificado consumo de benzodiazepínicos no momento do estudo. Constatou-se que 20 por cento dos entrevistados tinham antecedentes de consumo de benzodiazepínicos e, destes, a metade (10 por cento), no último ano. A análise bivariada do consumo de benzodiazepínicos no último ano com variáveis relacionadas ao trabalho mostrou uma relação pouco significativa (p= 0,073) com jornada de trabalho. Não foi identificada associação entre o consumo de benzodiazepínicos e as variáveis sócio-demográficas entre os participantes deste estudo.

Effects of estrogen, clomiphene on gamma-aminobutyric acid immunoreactive cell and ?1 subunit of GABA_A receptor in hippocampus of epileptic rats / 中华神经科杂志

Objectives To find out the effects of estrogen and clomiphene on behavior of epileptic rats induced by kainic acid (KA) and probe into some mechanisms. Methods Ovariectomized Sprague-Dawley female rats were treated with estrogen (E) or estrogen and clomiphene (C). Their behaviors when they were induced seizures were observed and compared. Indirect immunofluorescence method was used to measure the alterations of gamma-aminobutyric acid (GABA) immunoreactive cells and ?1 subunits of GABA_A receptors in the hippocampus of all groups. Results The latency and time at reaching 4/5 degrees in KA+E group ((24.63?11.44) minutes and (41.50?16.22) minutes, respectively) were reduced greatly than KA group ((46.75?14.61) minutes and (65.13?12.99) minutes), while the latency of (KA+)E+C group (adding estrogen and clomiphene, (43.50?5.75) minutes) became prolonged significantly than in KA+E group. Conclusion High-level estrogen should be proconvulsant and the clomiphene might have some antiepileptic effects, which may be related with some alterations of GABA energic function in the brain.

Effects of fentanyl on GABAA receptor in rat hippocampal pyramidal neurons / 中华麻醉学杂志

Objective To investigate the inhibitory effects of fentanyl on GABAA receptors in hippocampal pyramidal neurons of rat.Methods Pyramidal neurons were acutely isolated from 3-10 day old SD rats of either sex by enzymatic-mechanic method. GABAA receptor mediated currents ( IGABA) were recorded using voltage clamped whole cell patch clamp technique in gap-free mode at the holding potential (VH) of - 50 mV. Current-voltage relationship of IGABA was obtained in ramp protocol ranging from + 30 mV to - 110 mV and lasting for 1 600 ms. Data were collected by using a system consisting of Axopatch 200B patch-clamp amplifier, Pentium Ⅲ computer and Digidata 1200 interface. All experiments were performed at room temperature (22-25℃). Five to twelve neurons were used for each fentanyl concentration. The effects of fentanyl from 1.0 ? 10-5 ?mol?L-1 to 10. 0 ?mol?L-1 were evaluated by the inhibition rate of the peak amplitude of IGABA, the desensitization time constant (?des) of IGABA and the reversal potential (Ecl- ) of IGABA. A ?-opioid receptor selective antagonist CTAP 1 ?mol?L-1 was applied and its effects on fentanyl were recorded. Results (1) GAB A 1-1 000 ?mol?L-1 induced inward currents (IGABA) dose-dependently with an EC50 of 23.73 ?mol?L-1.IGABA induced by GABA 30 ?mol?L-1 was blocked by bicuculline 1 ?mol?L-1. (2) Fentanyl depressed IGABA dose-dependently with EC50 of 0.011 ?mol?L-1 and shortened the rdes of IGABA.(3) The inhibitory effects of fentanyl on IGABA were antagonized by CTAP. (4) Fentanyl 0.01 ?mol?L-1 and CTAP did not influence the reversal potential of IGABA (Ecl- -3.0 mV) .Conclusion Fentanyl inhibits the function of GABAA receptors through ?-opioid receptors in hippocampal pyramidal neurons. Hippocampus may play a role in the neuroexcitatory effects of opioids.