Research progress of effect of anxiolytic traditional Chinese medicines and formulas on neurotransmitters / 中国中药杂志

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.

Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

The elevated gradient of aversion: a new apparatus to study the rat behavior dimensions of anxiety, fear, and impulsivity

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

ABSTRACT Membrane/lipid rafts (MLRs) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (statins) can disable the N-methyl-D-aspartate (NMDA) receptor through disruption of MLRs and, in turn, decrease NMDA-mediated anxiety. This hypothesis will contribute to understanding the critical roles of simvastatin in treating anxiety via the NMDA receptor.

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats

The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.

The effects of bromazepam over the central and frontal areas during a motor task: an EEG study / Os efeitos do bromazepam nas áreas corticais central e frontal durante execução de uma tarefa motora: um estudo de EEG

The present study investigates the influence of bromazepam while executing a motor task. Specifically, we intend to analyze the changes in alpha absolute power under two experimental conditions, bromazepam and placebo. We also included analyses of theta and beta frequencies. We collected electroencephalographic data before, during, and after motor task execution. We used a Two Way ANOVA to investigate the condition (PL × Br6 mg) and moment (pre and post) variables for the following electrodes: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, CZ and C4. We found a main effect for condition on the electrodes FP1, F7, F3, Fz, F4, C3 and CZ, for alpha and beta bands. For beta band we also found a main effect for condition on the electrodes Fp2, F8 and C4; for theta band we identified a main effect for condition on C3, Cz and C4 electrodes. This finding suggests that the motor task did not have any influence on the electrocortical activity in alpha, and that the existing modifications were a consequence due merely to the drug use. Despite its anxiolytic and sedative action, bromazepam did not show any significant changes when the individuals executed a finger extension motor task.

O presente estudo investiga a influência do bromazepam durante a execução de uma tarefa motora. Especificamente, pretende-se analisar as mudanças na potência absoluta de alfa sob duas condições experimentais, bromazepam e placebo. Nós também incluímos as analises das frequências teta e beta. Foram coletados dados eletroencefalográficos antes, durante e depois da execução da tarefa motora. Usamos uma Anova de 2 fatores para investigar a condição (PL × Br6 mg) e variáveis no momento (pré e pós) para os seguintes eletrodos: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, C4 e CZ. Encontramos um efeito principal para a condição e eletrodos FP1, F7, F3, Fz, F4, C3 e CZ para alfa e beta. Para beta também foi encontrado um efeito principal para condição nos eletrodos Fp2, F8 e C4; para theta nós identificamos um efeito principal para condition em C3, Cz e C4. Este achado sugere que a tarefa motora não tem qualquer influência sobre a atividade eletrocortical alfa e que as modificações existentes foram uma consequência devido o uso de drogas. Apesar de sua ação ansiolítica e sedativa, o bromazepam não apresentou mudança significativa quando os indivíduos executaram uma tarefa motora.

Antidepressant and anxiolytic-like effects of essential oil from Acantholippia deserticola Phil in female rats / Efecto ansiolítico y antidepresivo del aceite esencial de Acantholippia deserticola Phil en ratas hembras

Acantholippia deserticola (Phil.ex F. Phil.) Moldenke is a Verbenaceae that has long been used in traditional medicine in Tarapacá (Chile) as an analgesic, anti-inflammatory and aphrodisiac agent. Sincé alpha - and beta -thujone were identified as the main constituents (88.4 percent) of the essential oil from this plant, we investigated its biological properties. The results show that the essential oil from Acantholippia deserticola decreased locomotive and rearing activity compared to control group rats, including those treated with diazepam, but the essential oil had no effects on head movements or grooming. The essential oil also had significant anxiolytic and antidepressant effects. This essential oil, therefore, has sedative, anxiolytic and antidepressant actions on the rat central nervous system.

Acantholippia deserticola es una Verbenaceae de uso en la medicina tradicional como analgésico, antiinflamatorio y afrodisíaco en la región de Tarapacá, Chile. En el aceite esencial se ha identificado alfa - and beta -tuyonas como principales constituyentes (88.4 por ciento) de esta planta, que ha llevado a investigar sus propiedades biológicas. Los resultados muestran que el aceite esencial de Acantholippia deserticola disminuye la locomoción y el levantamiento en dos patas, en comparación con el grupo control, incluido el tratado por el diazepam, pero el aceite esencial no tuvo efecto sobre la sacudida de cabeza y el acicalamiento. En ambas pruebas, se observa un efecto significativo del aceite esencial en los efectos ansiolíticos y antidepresivos, lo que indica que el aceite esencial tiene actividad sedante, ansiolítica y antidepresiva en el sistema nervioso central.

Anxiolytic-like effect of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) in experimental mouse models of anxiety.

The present research was designed to explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (6o) in experimental mouse models of anxiety. The anxiolytic activity of '6o' at (1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark aversion test, hole board (HB) and open field test (OFT) with diazepam (2 mg/kg, ip) as a standard anxiolytic. None of the tested doses of '6o' affected the base line locomotion. Compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the percentage of both time spent and open arm entries in the EPM test. Compound '6o' in (1 mg/kg, ip) dose was only able to affect the percentage time spent in open arm significantly in the EPM test. In the light and dark test, compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the total time spent in light compartment as well as number of transitions from one compartment to other and number of square crossed. Compound '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) also significantly increased number of head dips and number of squares crossed, whereas significantly decreased the head dipping latency in HB test as compared to vehicle control group. In addition, '6o' in both the doses and diazepam (2mg/kg, ip) significantly increased the ambulation scores (squares crossed) in OFT however, there was no significant effect of '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) on rearing scores. To conclude compound '6o' exhibited an anxiolytic-like effect in animal models of anxiety.

Anxiolytic-like effect of etazolate, a type 4 phosphodiesterase inhibitor in experimental models of anxiety.

Etazolate is a selective inhibitor of type 4 phosphodiesterase (PDE4) class enzyme. Antidepressant-like effect of etazolate has been previously demonstrated in the rodent models of depression. The present study was designed to investigate the anxiolytic-like activity of etazolate in experimental mouse models of anxiety. The putative anxiolytic effect of etazolate (0.25-1 mg/kg, ip) was studied in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark (L/D) aversion, hole board (HB) and open field (OFT) with diazepam (2 mg/kg, ip) as reference anxiolytic. Like diazepam (2 mg/kg, ip), etazolate (0.5 and 1 mg/kg, ip) significantly increased the percentage of both time spent and entries into open arms in the EPM test. In the L/D test etazolate (0.5 and 1 mg/kg, ip) increased the both total time spent in and latency time to leave the light compartment. Etazolate (0.5 and 1 mg/kg, ip) also significantly increased head dipping scores and time spent in head dipping, whereas significantly decreased the head dipping latency in HB test. In addition, etazolate (0.5 and 1 mg/kg, ip) significantly increased the ambulation scores (square crossed) and number of rearing in OFT. In conclusion, these findings indicated that etazolate exhibited an anxiolytic-like effect in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.

Neurochemical and behavioral effects of green tea [Camellia sinensis]: a model study

Being rich in polyphenolic compounds such as flavonoids, green tea is suggested to be a potential candidate for the treatment of obesity, stress, depression, Parkinson's and other disorders. Since serotonin has an important role in the pathophysiology of these disorders, present study was designed to monitor the effects of green tea in rats. Green tea extract was provided to the male Albino Wistar rats for 5 weeks, and effects on behaviors were monitored. Results show a decrease in food intake after 5th week but not before. An increase in locomotive activities of the animals was observed, as monitored in novel as well as in familiar environment. Anxiolytic effects were observed in elevated plus maze but not in light dark activity box. An increase in dopamine and serotonin turnover was observed. Our results suggest that beneficial effects of green tea drinking might be due to alteration of serotonin and/or dopamine metabolism. We thereby propose that in further experiments, green tea should be administered in animal model of learned helplessness and effects on the development of adaptation to stress should be monitored. Neurochemical estimations of catecholamine and indoleamine in these animal models of stress exposed to green tea would help in understanding the anxiolytic effects of green tea

Pharmacological evaluation of Antidesma ghaesembilla Gaertn fruits for central nervous system depressant activity / Evaluación farmacológica de frutos de Antidesma ghaesembilla Gaertncomo depresores del sistema nervioso central

The objective of this study is to investigate the anxiolytic and sedative activities of the methanol and chloroform extracts of Antidesma ghaesembilla fruits at the dose of 400 mg/kg bw using rodent behavioral models such as thiopental sodium-induced sleeping time, hole cross method and open field process for sedative and its anxiolytic activity was evaluated using the elevated plus maze (EPM) methods. In case of thiopental sodium-induced sleeping time, both extracts exhibited dose dependent suppression of motor activity, exploratory behavior (in open field and hole cross method) and prolongation of thiopental sodium-induced sleeping time in mice, where maximum effect was shown by the methanol extract. In EPM test, the methanolic extract significantly increased exploration to and time spent by the treated mice in EPM open arms in a way similar to that of diazepam, but the chloroform extract was found to produce moderate activity. These significant results may justify the scientific basis for use of this plant in traditional medicine as a modality for anxiety and related disorders.

El objetivo de este estudio fue la investigación de las actividades ansiolíticas y sedantes de los extractos clorofórmicos y metabólicos de los frutos de Antidesma ghaesembilla a las dosis de 400 mg/kg pp utilizando modelos de comportamiento de roedores, tales como el tiempo de sueño inducido por tiopental sódico, el método de “hole cross” (cruce de un agujero) y el campo abierto para evaluar sedación, y la actividad ansiolítica fue evaluada utilizando el método del laberinto elevado (elevated plus maze, EPM). En el caso del sueño inducido por tiopental sódico, ambos extractos exhibieron una supresión dosis dependiente de la actividad motora, de la actividad exploratoria (en el método de campo abierto y “hole cross”) y prolongación del tiempo de inducción de sueño inducido por tiopental en ratones, con efectos máximos mostrados para el extracto metabólico. En el ensayo de EPM, el extracto metabólico aumentó significativamente el tiempo de exploración y el tiempo consumido en el laberinto de una manera similar al diazepam, pero el extracto clorofórmico se encontró que produjo solo una moderada actividad. Estos resultados significativos pueden justificar una base científica para el uso de plantas en medicina tradicional para tratar la ansiedad y desórdenes relacionados.

Combinación de tratamientos y complementariedad terapéutica en los trastornos de ansiedad / Combined treatment and therapeutic complementary for the anxiety disorders

El presente artículo revisa la literatura científica referida a la combinación entre tratamientos farmacológicos y psicosociales en los trastornos de ansiedad. Se reseñan aquellos estudios que han realizado la evaluación empírica de la combinación de tratamientos con el mayor rigor metodológico a través de las bases de datos de PubMed y PsycINFO. A partir de los ensayos realizados, se observa que la información disponible acerca de la ventaja del tratamiento combinado por encima de algún tipo de monoterapia, parece ser bastante controvertida y no concluyente en la mayoría de los trastornos de ansiedad. Esto puede observarse en los ensayos realizados sobre el trastorno por pánico con y sin agorafobia, el trastorno de ansiedad social y el trastorno de ansiedad generalizada. Se observa un déficit de investigación en general pero particularmente en la fobia específica, para la cual no encontramos estudios comparativos. En el tratamiento del trastorno por estrés postraumático, sólo se considera la combinación cuando la psicoterapia no haya alcanzado sus objetivos, y en el abordaje del trastorno obsesivo-compulsivo es donde contamos con evidencia aunque bastante limitada acerca de la superioridad del tratamiento combinado sobre la monoterapia. Se comentan las implicaciones clínicas de estos estudios.

Avanços no estudo da atividade ansiolítica do panax ginseng C. A. Meyer: [revisão] / Advances in the study of anxiolytic activity of panax ginseng C. A. Meyer: [review]

To focus on the current evidence on the anxiolytic activity of Panax ginseng C.A Meyer. Recent studies showed the anxiolytic effects of the constituents of the roots of this species. Triterpenoid saponins of ginseng known as ginsenosides, are the active chemical components of the roots of this plant likely related to its anxiolytic activity. The interaction of these components with ligands of GABA receptor, increasing its affinity for the receptor, decreased production of mRNA catabolic enzyme (Abat) and this inhibitory neurotransmitter GABA transporter (GAT1) are related events so far to the anxiolytic effect of ginseng.Both the white ginseng and red ginseng have anxiolytic properties.

Estudo enfoca as atuais evidências sobre a atividade ansiolítica do Panax ginseng C.A Meyer. Recentes pesquisas evidenciaram os efeitos ansiolíticos dos constituintes das raízes desta espécie. Saponinas triterpenóides de ginseng, conhecidos como ginsenosídeos, são os componentes químicos ativos das raízes desta planta relacionados à sua provável atividade ansiolítica. A interação destes constituintes com ligantes do receptor GABA, aumentando a sua afinidade pelo receptor, a diminuição da produção de RNAm da enzima catabólica (Abat) deste neurotransmissor inibitório e do transportador GABA (GAT1) são eventos relacionados até o momento ao efeito ansiolítico do ginseng. Tanto o ginseng branco como o ginseng vermelho apresentam propriedades ansiolíticas.

Chemical composition of the essential oil from kelussia odoratissima mozaff. and the evaluation of its sedative and anxiolytic effects in mice

OBJECTIVE: The present study aimed to evaluate the sedative and anxiolytic effects of the essential oils and hydroalcoholic extract of Kelussia odoratissima Mozaff. (K. odoratissima) in mice by utilizing an elevated plus maze. The chemical composition of its essential oil was also determined. METHODS: The hydroalcoholic extract or essential oil fraction from this plant were administered intraperitoneally to male mice at various doses 30 min before testing. The anxiolytic and sedative effects were determined by an elevated plus maze and locomotor activity tests, respectively. RESULTS: According to the results, none of the administered doses of hydroalcoholic extract or essential oil fraction of K. odoratissima changed the percentage of the time spent or number of entries into the open arms of the elevated plus maze. In contrast, the cumulative spontaneous locomotor activity of mice treated with the essential oil or hydroalcoholic extract was significantly decreased. Chemical analysis of the essential oil by Gas chromatography-mass spectromentry (GC-MS) showed that 3-butylidene-4,5-dihydrophthalide (85.9 percent) was the major component. CONCLUSION: These data confirm the sedative properties of K. odoratissima, yet there were no profound anxiolytic effects observed.

Evaluation of the acute and subchronic oral toxicity of ethanol extract from Valeriana pavonii species in Wistar rats / Evaluación de la toxicidad oral aguda y sub-crónica del extracto etanólico de la especie Valeriana pavonii en ratas Wistar

Introduction: One of the most frequent problems found in medicinal plants is the absence of clinical, toxicological, and pharmacological studies. Valeriana pavonii is one of the species used in Colombia as an anxiolytic. Further study of this specie is rendered to add information in the toxicological area. Objective: The acute and subchronic oral toxicity of V. pavonii ethanolic extract was evaluated in Wistar rats of both sexes. Materials and methods: The rats were distributed into four groups: the control group received the vehicle (0.5 mL/100 g of corporal weight) and the other three groups received increasing levels of the dosage for 90 days to evaluate characteristics like physical exam, laboratory test (blood chemistry and haematology), and anatomopathological findings. Results: This study reveals that there were no signs of toxicity, mortality, or significant alterations attributable to the ethanolic extract of V. pavonii. Conclusions: The Not Observed Adverse Effect Levels (NOAEL) of V. pavonii ethanolic extract were 2000 and 1000 mg/kg of body weight for the acute and subchronic toxicity studies, respectively.

Introducción: Uno de los problemas más frecuentes asociados con el uso de plantas medicinales es la ausencia de evidencias farmacológicas, toxicológicas y clínicas. Valeriana pavonii es una de las especies más utilizadas popularmente en Colombia con fines ansiolíticos. Es necesario avanzar en el estudio de esta especie para aportar información en el campo toxicológico. Objetivos: Evaluar la toxicidad oral aguda y sub-crónica del extracto etanólico de V. pavonii en ratas Wistar de ambos sexos. Materiales y métodos: En cada uno de los estudios se distribuyeron ratas en cuatro grupos; un grupo control que recibió únicamente vehículo (0.5 ml/100 g de peso corporal) y tres grupos correspondientes a niveles crecientes de dosis, así: para el estudio de toxicidad aguda se administraron en dosis única 20, 200 y 2000 mg/kg con un período de observación de 14 días y para el de toxicidad sub-crónica, dosis diarias de 250, 500 y 1000 mg/kg durante 90 días. Se evaluaron los parámetros de examen físico, los exámenes de laboratorio (química sanguínea y hematología) y el estudio anatomopatológico. Resultados: No se presentaron signos de toxicidad, letalidad ni alteraciones significativas atribuibles al consumo del extracto etanólico de V. pavonii, según el examen físico, el examen anatomopatológico y el análisis de las pruebas de química sanguínea y hematología. Conclusiones: Los valores de nivel sin efectos adversos observados (NOAEL) del extracto etanólico de V. pavonii, fueron 2000 y 1000 mg/kg de peso corporal para los estudios de toxicidad aguda y sub-crónica, respectivamente. No se encontraron valores de nivel más bajo de efecto adverso observado (LOAEL).

Absence of sibutramine effect on spontaneous anxiety in rats / Ausência de efeito da sibutramina na ansiedade espontânea em ratos

INTRODUSTION: Sibutramine has been described as a drug recommended for treatment of obesity, since it has the ability to inhibit the reuptake of serotonin and noradrenaline in the central nervous system, thereby increasing energy expenditure. OBJECTIVE: Investigate the anxiogenic and anxiolytic effects of acute and chronic treatment with sibutramine in rats submitted to the task of the elevated plus-maze. METHODS: Diazepam was used as a positive control for the anxiolytic effect, and the task of the elevated plus-maze showed sensitivity to detect the effect. In the chronic treatment, sibutramine was ingested for a period of two months. RESULTS: The acute and chronic treatments at the studied dose, which is described to produce a maximum effect of anti-obesity in rats, did not interfere with anxiety. CONCLUSIONS: The acute and chronic administration of sibutramine is not related to anxiolytic or anxiogenic effects.

INTRODUÇÃO: A sibutramina tem sido descrita como um fármaco recomendado para o tratamento da obesidade, uma vez que tem a capacidade de inibir a recaptação de serotonina e noradrenalina no sistema nervoso central, aumentando assim o gasto energético. OBJETIVO: Investigar os efeitos ansiogênico e ansiolítico dos tratamentos agudo e crônico com a sibutramina em ratos Wistar submetidos à tarefa do labirinto em cruz elevado. MÉTODOS: O diazepam foi usado como controle positivo para o efeito ansiolítico, e a tarefa do labirinto em cruz elevado apresentou sensibilidade para detectar o efeito. No tratamento crônico, a sibutramina foi ingerida por um período de dois meses. RESULTADOS: Os tratamentos agudo e crônico, na dose estudada, que é descrita para produzir um efeito de antiobesidade máxima em ratos, não interferem na ansiedade. CONCLUSÕES: As administrações aguda e crônica de sibutramina não estão relacionadas aos efeitos ansiolítico ou ansiogênico.

An extract of neem leaves reduces anxiety without causing motor side effects in an experimental model / Un extracto de hojas de neem reduce la ansiedad sin causar efectos colaterales motores en un modelo experimental

Anxiety modulation often requires pharmaceutical intervention, and though effective in the short term, benzodiazepines may cause impaired motor function. As a potential alternative, anxiety-modulating effects of a neem leaf (Azadirachta indica, A Juss) extract were investigated using ethological analysis of rat behaviour on an elevated X maze and compared with diazepam treatment. Sexually immature female Sprague-Dawley rats received 0.07 or 7 mg/kg neem leaf steroidal extract, a sham injection, a 1% DMSO/saline vehicle, 2 mg/kg diazepam or no treatment one hour prior to a recorded five-minute exploration of the elevated X maze. Neem matched diazepam in anxiety reduction as both treatments caused a decrease in per cent protected stretched-attend postures (PPSAP). Neem treatment had no effect on closed arm entries or total rears, distinguishing it pharmacologically from diazepam which resulted in a predictable decrease in those locomotor measures. Whereas both neem and diazepam reduced anxiety in complex ethological behavioural indices, only neem produced anxiolysis without motor deficiency.

La modulación de la ansiedad requiere a menudo la intervención farmacéutica, y aunque eficaz a corto plazo, las benzodiazepinas pueden afectar la función motora. Como una alternativa potencial, los efectos moduladores de la ansiedad obtenidos a partir de un extracto de la hoja de neem (Azadirachta indica, A Juss), fueron investigados mediante análisis etiológico del comportamiento de ratas en un laberinto x elevado, y comparados con el tratamiento con diazepam. Ratas Sprague-Dawley hembras, sexualmente inmaduras, recibieron 0.07 ó 7 mg/kg de extracto esteroidal de hojas de neem, una inyección simulada, un vehículo salino de DMSO al 1%, 2 mg/kg de diazepam o ningún tratamiento una hora antes de registrarse una exploración de cinco minutos en el laberinto X elevado. El neem igualó al diazepam en la reducción de ansiedad, ya que ambos tratamientos causaron una disminución en las posturas de atención extremada protegida porcentual (PPSAP). El tratamiento de Neem no tuvo efecto sobre las entradas al brazo cerrado o actividades aéreas (con las patas traseras) distinguiéndose así farmacológicamente del diazepam que producía una disminución predecible en esas medidas locomotoras. Si bien tanto el neem como el diazepam reducían la ansiedad en los índices conductuales etológicos complejos, solamente el neem producía ansiolisis sin deficiencias motoras.

Correlation between function-morphology of effect of the stress and flunitrazepam administered during gestation in adult mouse ovary / Correlación entre la función y la morfología de los efectos de estrés y flunitrazepam administrado durante la gestación en ovario de ratón adulto

Previously we report long lasting effects on ovary of mice prenatally exposed to flunitrazepam (FNZ), a benzodiazepine with tranquilized action. In this work we find that the FNZ don't prevent the effects on ovary prenatally exposure to stress in mice. We studied adult females born from mothers that had been stressed by immobilization on day 6 ofgestation (GD-6) or group S, and from mothers stressed also by immobilization at GD-6, but which received a single oral dose of FNZ immediately after the stress group FNZS. The control groups were the SS that received the GD-6 saline solution and the group NT non-treated. Their ovaries were extracted for histology studies and to observe the activity of 3b hydroxysteroid dehydrogenase/isomerase (3 b-HSD). The histological analysis revealed high staining affinity ovarian cell of S and FNZS. Double oocytes and apoptotic bodies were found in the secondary atretic follicles, as well as abnormal primordial, primary and secondary follicle populations, as compared to SS and NT groups. The primordial, primary, and secondary follicles were significantly reduced in the experimental groups. But the primary and secondary atretic follicles were higher in both groups, and the number of corpora lutea was lower in both groups. The activity of 3 b-HSD was abnormally increased in both FNZS- and S-groups. These findings suggest that FNZ did not counteract the impairing effects of prenatal stress on adult offspring ovarian follicles, and could rather be responsible for long lasting changes occurring during embryonic programming.

Previamente comprobamos efectos de larga duración sobre el ovario de ratones expuestos prenatalmente a flunitrazepam (FNZ), una benzodiazepina con acción tranquilizante. En este trabajo encontramos que el FNZ, no revierte los efectos producidos por la exposición prenatal a estrés. Estudiamos hembras adultas nacidas de madres que se estresaron por inmovilización el día 6 de la gestación (DG-6) o grupo S, y de madres estresadas también por inmovilización el DG-6, las que recibieron una sola dosis de FNZ inmediatamente después del estrés (grupo FNZS). Los grupos de control fueron el SS al que se le administró solución salina y el NT no tratado. Se extrajeron sus ovarios para su estudio histológico y para observar la actividad de delta 3b-deshidroxiesteroide dehidrogenasa/isomerasa (3 b-HSD). El análisis histológico reveló una gran afinidad tintoreal en los ovarios de los grupos S y FNZS. En los ovarios de los ratones del grupo FNZS se encontraron en los folículos secundarios atrésicos ovocitos dobles y cuerpos apoptóticos así como una población mayor de folículos anormales primordiales, primarios y secundarios en comparación con los grupos SS y NT. Los folículos primarios y secundarios tuvieron una reducción significativa en los grupos experimentales pero los folículos atrésicos primarios y secundarios fueron más en ambos grupos y el número de cuerpos lúteos fue menor en ambos grupos. La actividad de 3 b-HSD aumentó de manera anormal tanto en los grupos FNZ y S. Estos hallazgos sugieren que el FNZ no contrarresta los efectos negativos del estrés prenatal sobre los folículos ováricos de las crías adultas, y podría ser responsable de los cambios largo plazo que ocurren a durante la programación embrionaria.

Preconditioning abolishion by midazolam in isolated hearts of rats / Abolição do precondicionamento pelo midazolam em corações isolados de ratos

PURPOSE: To study the effects of benzodiazepine midazolam in the coronary flow (Cflo), cardiac frequency (CF) and myocardial contractility in isolated hearts of rats subjected to ischemic preconditioning (IPC). METHODS: 30 Wistar rats were used, undistinguished by gender. After anesthesia with ethyl ether, the hearts were put into perfusion (Krebs-Henseleit solution, 95 percent O2 and 5 percent CO2, 37°C, 110-120mmHg), in disposable Langendorff type system. Five groups of six animals were constituted: GI- Control; GII- Ischemia; GIII- IPC; GIV- Ischemia + 100mcg of midazolam; GV- IPC + 100mcg of midazolam. After stabilization (t0), and on times t5, t10, t15, t20 and t25, CF, Cflo, systolic pressure (SP) and diastolic pressure (DP) and dP/dt were recorded. DP was maintained at 5 ± 2 mmHg. The statistical method ANOVA and Tukey Test were employed for p < 0.05. RESULTS: No significant variations have occurred between Cflo and CF. On Pd/td, differences have occurred (p<0.05) between groups I and II (respectively 94.7±23.0 and 62.3±12.1 percent). The preconditioning (GIII), improved significantly the results in the group II (respectively 62.3±12.1 and 87.1±12.4 percent). The decrease in dP/dt in group II was not prevented by midazolam (GIV) (62.3±12,1 and 60.5±15.8 percent). In group III, dP/dt was 87.1±12.4 percent, whereas in group V, only 55.5±17.2 percent (p<0.05) CONCLUSION: Midazolam, when administered before the ischemia, was unable to prevent the ischemic deterioration of the myocardium. When administered before the preconditioning, it has abolished its protective effect.

OBJETIVO: Estudar os efeitos do benzodiazepínico midazolam no fluxo coronariano (Fco), freqüência cardíaca (FC) e contratilidade miocárdica de corações isolados de ratos submetidos ao precondicionamento isquêmico (PCI). MÉTODOS: Foram utilizados 30 ratos Wistar sem distinção de sexo. Após anestesia com éter etílico, os corações foram postos em perfusão (solução de Krebs-Henseleit, 95 por cento de O2 e 5 por cento de CO2, 37°C, 110-120mmHg), em sistema tipo Langendorff descartável. Foram constituídos cinco grupos de seis animais: GI- Controle; GII- Isquemia; GIII- PCI; GIV- Isquemia + 100mcg de midazolam ; GV- PCI + 100mcg de midazolam. Após estabilização (t0), e nos tempos t5, t10, t15, t20 e t25, foram registrados a FC, Fco, pressões sistólica (PS) e diastólica (PD) e dP/dt. A PD foi mantida em 5 ± 2 mmHg. Empregou-se método estatístico ANOVA e Teste de Tukey para p < 0,05. RESULTADOS: Não ocorreram variações significantes entre FCo e FC. Na dP/dt, ocorreram diferenças (p<0,05) entre os grupos I e II (respectivamente 94,7±23,0 e 62,3±12,1 por cento). O precondicionamento (GIII), melhorou significantemente os resultados do grupo II (respectivamente 62,3±12,1 e 87,1±12,4 por cento). A queda da dP/dt no grupo II não foi impedida pelo midazolam (GIV) ( 62,3±12,1 e 60,5±15,8 por cento). No grupo III a dP/dT foi 87,1±12,4 por cento, sendo que no grupo V, apenas 55,5±17,2 por cento (p<0,05). CONCLUSÃO: O midazolan quando administrado antes da isquemia não impediu deterioração isquêmica do miocárdio. Quando administrado antes do precondicionamento aboliu seu efeito protetor.