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Orientador(a): Profa. Dra. Marcela Bermudez Echeverry Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós Graduação em Neurociência e Cognição. São Bernardo do Campo, 2021 Antipsicóticos típicos, como o haloperidol, tem por mecanismo de ação principal a capacidade de bloquear receptores dopaminérgicos do tipo D2 (D2R) no sistema nervoso central. Esses fármacos são a principal estratégia terapêutica de uma série de transtornos psiquiátricos e neurológicos, dentre eles, a esquizofrenia. Infelizmente esses medicamentos têm sido exaustivamente associados a efeitos colaterais motores debilitantes, os sintomas extrapiramidais, que podem ser divididos em alterações hipercinéticas (como a discinesia tardia; ou vacuous chewing movements (VCMs), em modelos animais) e hipocinéticas (como o parkinsonismo; ou catalepsia, em animais experimentais). Estudos prévios mostram que a metoclopramida, uma droga antiemética que é também antagonista de D2R, pode ser capaz de induzir efeitos extrapiramidais em humanos e roedores, de modo similar ao haloperidol. Esse trabalho teve por objetivo avaliar os efeitos comportamentais da exposição crônica à metoclopramida (5 mg/kg ou 8 mg/kg) e haloperidol (0.5 mg/kg) em camundongos suíços, e posteriormente avaliar a modulação na imunorreatividade da proteína ?FosB, um fator de transcrição associado a mudanças neuronais de longo prazo em decorrência de estímulos extracelular crônicos, já relacionado a indução de efeitos extrapiramidais por antipsicóticos. Além disso, com o objetivo de avaliar a participação do sistema nitrérgico, realizamos a quantificação da proteína nNOS. As avaliações histoquímicas foram realizadas no estriado, a principal estrutura dos núcleos da base. Observamos que a metoclopramida, assim como o haloperidol, induz catalepsia e a manifestação de VCMs e, além disso, modulam comportamentos exploratórios e motivacionais/emocionais. A nível biológico, houve aumento na imunorreatividade para ?FosB na região motora do estriado (dorsolateral), mas não nas demais regiões, para o haloperidol e para a metoclopramida na dose de 5 mg/kg. Observamos também que a exposição crônica ao haloperidol ou à metoclopramida em camundongos suíços não altera a marcação de nNOS em nenhum dos quadrantes estriatais. Esses dados sugerem que maior atenção deve ser dada a utilização indiscriminada de metoclopramida, sobretudo ao que se refere as doses utilizadas e ao tempo de exposição. First-generation antipsychotics, such as haloperidol, have as their main mechanism of action the ability to block D2-like dopaminergic receptors type (D2R), in the central nervous system. These drugs are the main therapeutic strategy for a series of psychiatric and neurological disorders, including schizophrenia. Unfortunately, these medications have been extensively associated with debilitating motor side effects, the extrapyramidal symptoms, which can be divided into hyperkinetic (such as tardive dyskinesia; or vacuous chewing movement (VCMs), in animal models) and hypokinetic (such as parkinsonism; or catalepsy, in experimental animals) dysfunctions. Previous studies show that metoclopramide, an antiemetic drug that is also a D2R antagonist, may be able to induce extrapyramidal effects in humans and rodents, similarly to haloperidol. This work aimed to evaluate the behavioral effects of chronic exposure to metoclopramide (5 mg/kg or 8 mg/kg) and haloperidol (0.5 mg/kg) in Swiss mice and later to evaluate the modulation in the immunoreactivity of the ?FosB protein, a transcription factor associated with long-term neuronal changes after chronic extracellular stimuli, already related to the induction of extrapyramidal effects by antipsychotics. Furthermore, to evaluate the participation of the nitrergic system, we quantified the nNOS protein. Histochemical evaluations were performed in the striatum, the main structure of the basal ganglia. We observed that metoclopramide, like haloperidol, induces catalepsy and VCMs and, in addition, modulates exploratory and motivational/emotional behaviors. At the biological level, there was an increase in ?FosB immunoreactivity in the motor region of the striatum (dorsolateral), for haloperidol, and metoclopramide at the dose of 5 mg/kg. We also observed that chronic exposure to haloperidol or metoclopramide does not alter the ?FosB labeled cells in the other regions or nNOS in any of the striatal quadrants in Swiss mice. These data suggest that greater attention should be paid to the indiscriminate use of metoclopramide, especially regarding the doses used and the exposure time.

Ipomoea pes-caprae (Convolvulaceae), popularly known as “salsa-da-praia”, is used in folk medicine for the treatment of several diseases, including hypertension. The aim of this research was to evaluate hypotensive activity attributed to this species and identify the bioactive compounds responsible for this effect. Hydroalcoholic extract of aerial parts of Ipomoea pes-caprae (PIEA) was fractionated by column chromatography with Amberlite XAD-2, thus achieving a methanolic fraction (PIEA-M). The chemical profile investigation of PIEA-M was conducted by Ultra Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS) and compound isolation through High Performance Countercurrent Chromatography (HPCCC). Hemodynamic evaluations of PIEA, PIEA-M and isolated compounds were carried out on normotensive rats. The locomotor activity of PIEA and PIEA-M were performed by Rota Rod test using Swiss mice. UPLC-MS analysis of PIEA-M led to the identification of 11 compounds corresponding to seven phenolic acids and four flavonoids. By means of HPCCC, quercetin 6”-O-acetyl-3-O- glucoside (1), a mixture of quercetin-3-O-galactoside and quercetin-3-O- glucoside (2) and quercetin 3-O-glucoside (3) were isolated. PIEA, PIEA-M and the obtained compounds (1 and 2) significantly reduced blood pressure. Also, PIEA and PIEA-M caused significant impairment on mice locomotor activity. These results indicate the potential of Ipomoea pes-caprae as a source of hypotensive agents suggesting that phenolic compounds present in the species are responsible for its hypotensive activity. Resumo Ipomoea pes-caprae (Convolvulaceae), conhecida popularmente como “salsa-da-praia”, é usada na medicina popular para o tratamento de várias doenças, incluindo a hipertensão. O objetivo desta pesquisa foi avaliar a atividade hipotensora atribuída a essa espécie e identificar os compostos bioativos responsáveis por esse efeito. O extrato hidroalcoólico das partes aéreas de Ipomoea pes-caprae (PIEA) foi fracionado por cromatografia em coluna com Amberlite XAD-2, obtendo-se uma fração metanólica (PIEA-M). A investigação do perfil químico de PIEA-M foi realizada por Cromatografia :íquida de Ultra-Eficiência acoplada a Espectrometria de Massas (CLUE-EM) e isolamento de compostos por Cromatografia Contracorrente de Alto Desempenho (CCCAD). Avaliações hemodinâmicas dos PIEA, PIEA-M e compostos isolados foram realizadas em ratos normotensos. A atividade locomotora de PIEA e PIEA-M foi realizada pelo teste de Rota Rod usando camundongos suíços. A análise CLUE-EM do PIEA-M levou à identificação de 11 substâncias correspondentes a sete ácidos fenólicos e quatro flavonoides. Por meio de CCCAD, a quercetina 6”-O-acetil-3-O-glicosídeo (1), uma mistura de quercetina-3-O-galactosídeo e quercetina-3-O-glicosídeo (2) e quercetina 3-O-glicosídeo (3) foram isolados. PIEA, PIEA-M e as substâncias obtidas (1 e 2) reduziram significativamente a pressão sanguínea. Além disso, o PIEA e o PIEA-M causaram um prejuízo significativo na atividade locomotora dos camundongos. Estes resultados indicam o potencial de Ipomoea pes-caprae como fonte de agentes hipotensores, sugerindo que os compostos fenólicos presentes na espécie são responsáveis por sua atividade hipotensora.

This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.

Hücre içerisinde proteinleri kodlayan genlerin doğru ifade edilişi ve doğru katlanmış protein konsantrasyonu hücrenin yaşam döngüsünü devam ettirebilmesi için kritik öneme sahiptir. Nöronlarda proteostazın sağlanamadığı durumlarda patoloji oluşma riski artmaktadır. Son yıllarda, TDP-43 adı verilen proteinini kodlayan TARDP genindeki mutasyonların amiyotrofik lateral skleroz (ALS) ve frontotemporal lobar demans (FTLD) başta olmak üzere nörodejeneratif hastalıkları tetiklediği gösterilmiştir. Bu tez çalışmasında, insanlarda TDP-43 proteinini kodlayan gende üç farklı mutasyon oluşturularak, in utero elektroporasyon yöntemi ile sıçan embriyolarına aktarımı ile motor nöron hasarını taklit eden hayvan modellerinin oluşturulması ve meydana gelen değişikliklerinin davranış testleriyle değerlendirilmesi amaçlanmıştır. Motor nöronlarda hasar oluşturmak amacıyla iki farklı nokta mutasyonu (N276S ve A315T) ve NLS sinyali delesyona uğratılmış mutant TDP-43 geni kullanılmış ve bu genlerin motor nöronlarda uzun süreli ekspresyonu CBA (chicken β-actin) promotoru ile sağlanmıştır. Sprague-Dawley cinsi erişkin dişi sıçanlar (n=7) çiftleştirildikten sonra hamileliklerinin 16. gününde, amniyon kesesi içinde bulunan embriyolarının lateral ventrikülleri içine mutant DNA‟yı içeren plazmidler nanojektör ile enjekte edilmiştir. Enjeksiyon yapılmayan yavrular ise kontrol grubu olarak kullanılmıştır. Özel olarak dizayn edilmiş bir elektropod aracılığıyla DNA lateral ventrikülden motor kortekse doğru yönlendirildikten sonra batın usulüne uygun olarak kapatılmış ve gebe sıçanlar doğuma kadar kontrol koşullarında bakılmıştır. Gen aktarımı yapılan deney hayvanlarında motor fonksiyonları değerlendirmek amacıyla, postnatal (P) 90, 120, 150, 180 ve 300. günlerde olmak üzere, aktivitemetre, modifiye grip, rota-rod ve cat-walk yürüme testleri uygulanmış ve gruplar arası farklılıklar non-parametrik istatistiksel testler ile karşılaştırılmıştır. Sıçanların spontan lokomotor aktivitelerini değerlendirilmek amacıyla yapılan testlerde horizontal, ii vertikal, stereotipik ve toplam hareket sayıları ile test süresince ambulasyonda veya dinlenmede geçirdikleri zaman ve toplam kat ettikleri mesafelerde anlamlı bir farklılık gözlenmemiştir. Sadece P120‟de TDP-43 N267S grubundaki sıçanların toplam hareket sayıları kontrol grubundakilere kıyasla daha düşük bulunmuştur. Öte yandan rota-rod testindeki ortalama düşme sayıları karşılaştırıldığında; A315T mutasyon grubunda P120. günden itibaren, N276S mutasyon grubunda P150. günden itibaren, NLS delesyonunda ise P240. ve P300. günlerde olmak üzere düşme sayılarında kontrol gruplarına kıyasla anlamlı bir artış olduğu gözlenmiştir. Benzer şekilde mutasyonlu grupların modifiye edilmiş grip testindeki performans skorları karşılaştırıldığında da kontrol grubundaki deney hayvanlarına kıyasla daha düşük skorlar aldığı gözlenmiştir. Özellikle erken evrelerde (P90 ve P120) NLS delesyonlu TDP-43 grubu ile kontrol grubundaki sıçanların skorları arasında anlamlı farklılıklar saptanmıştır. P120. günde ise tüm mutasyon gruplarının grip testinde aldıkları skorların kontrol grubuna göre daha düşük olduğu gözlenmiştir. Cat-walk testinde ise sağ ve sol, ön ve arka olacak şekilde ardışık iki adım arası mesafe, aynı şekilde her bir ayak için maksimum ayak izi alanı ve ardışık iki adımın üst üste binme sıklığında gruplar arasında anlamlı bir fark gözlenmemiştir. Bu tez çalışmasında elde edilen sonuçlar, TDP-43 genomunda oluşturulan farklı mutasyonlar sonrasında, in utero elektroporasyon tekniği kullanılarak spesifik bir nöron popülasyonunda, belirlenen bir zaman dilimi içinde, hücre tipine özel hasarlanma oluşturabileceğini göstermektedir. Bu teknik, bu tez çalışmasında genetik risklere bağlı olarak eksprese edilen hatalı proteinlerin davranış düzeyindeki etkilerini araştırmak amacıyla kullanılmıştır. Ancak ileri çalışmalarda, motor nöronlarda meydana gelen morfolojik ve fonksiyonel değişikliklerin araştırılması amacıyla da kullanılması mümkündür. Proper expression of the genes encoding proteins and the right concentration of folded proteins in the cell are critical for maintaining the life cycle of cell. There is an increased risk of pathology in neurons when proteostasis cannot be achieved. In recent years, mutations in the TARDP gene encoding the protein called TDP-43 have been shown to trigger neurodegenerative diseases, primarily amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar dementia (FTLD). In this thesis study, generation of three different mutations in the gene encoding TDP-43 protein, their transfer to rat embryos via utero electroporation method and evaluation of phenotypic alterations via behavioral tests were aimed. In order to produce motor neuron damage, two different point mutations (N276S and A315T) and deletion of the NLS signal in the TDP-43 gene were used and the long-term expression of the genes was maintained by the CBA (chicken β-actin) promoter. After mating Sprague-Dawley adult female rats (n = 7), on the 17th day of their pregnancy, plasmids containing mutant DNA were injected into the lateral ventricles of the embryos growing inside of the amniotic sac via a nanojector. Pups without injection were used as a control group. By using a specially designed triple-electrode probe, DNA was directed from the lateral ventricle to the motor cortex and then abdominal layers were closed accordingly and pregnant rats were remained under control conditions until birth. In order to evaluate motor functions in animals, activity meter, modified grip, rota-rod and cat-walk walking tests were applied on postnatal days (P) 90, 120, 150, 180 and 300, and differences among groups were analyzed by non-parametric statistical tests. Spontaneous locomotor activities of rats were evaluated based on the number of horizontal, vertical, stereotypical and total movements, total traveled distance, ambulation and resting time, and no significant difference was observed among iv groups. However, only at P120, the total number of movements was lower in the N267S group than those of control group. On the other hand, when the mean number of falls in the rota-rod test was compared; there was a statistically significant increase in the A315T mutation group starting from P120, N276S mutation group starting from P150 and NLS deleted group at P240 and P300, in comparison to the control group. Similarly, in the modified grip test, mutation groups had lower scores than those of controls. Especially at the early stages (P90 and P120), significant differences were found between the scores of the TDP43 group with NLS deletion and the control group. Also that the scores of all mutation groups were lower than those of the control group in the modified grip test, at P120. In the cat-walk test, no significant difference was observed among the groups in terms of the parameters including; distance between two consecutive steps, right and left, front and back, as well as the maximum footprint area for each foot and the overlapping frequency of consecutive steps. The results obtained in this thesis study showed that various mutations in the TDP-43 genome might produce cell type-specific damages in a specific neuron population within a specified time frame using the in utero electroporation technique. In this thesis study, this technique has been used to investigate the effects of defective proteins expressed due to the genetic risks, at the behavioral level. However, in further studies, it is also a very useful method for investigation of the morphological and functional changes in motor neurons

WOS: 000374883700008, This study was planned to investigate possible antinociceptive activity of 1,5-diaryl-3-[4-(methylsulfonyl) phenyl]-4,5-dihydro-1H-pyrazole derivatives (2a-s), based on the analgesia-inducing potential of 4,5-dihydro-1H-pyrazole moiety carrying compounds. Tail-clip and hot-plate tests, measuring centrally organized responses to a noxious stimulus, were performed in order to examine antinociceptive potential of the test compounds (100 mg/kg, i.p). In addition, peripherally mediated antinociceptive effect was evaluated by acetic acid-induced writhing tests. Motor coordination of the animals was tested in a Rota-rod apparatus. Among the tested compounds 2c, 2e, 2g, 2h, 2j, 2l, 2m, 2o and 2r prolonged the reaction time, measured in the tail-clip and hot-plate tests, with respect to the control values. The same compounds also decreased the quantity of acetic acid-induced writhing behaviours. In the Rota-rod tests, compound 2r was the only derivative decreasing the falling latency of mice. The obtained results indicated that some of the tested 4,5-dihydro-1H-pyrazole derivatives induce notable antinociceptive activity by effecting both of the central and peripheral nociceptive pathways. In addition, this study provided some information about structure-activity relationship for the compounds carrying similar chemical scaffold. Nevertheless, it should be noted that mechanism of action for these agents should be clarified with further detailed investigations.

Bu çalışmanın amacıbenzotiyazol halkası taşıyan bazı bileşiklerin antinosiseptif veanksiyolitik-benzeri etkilerinin incelenmesidir. 40 mg/kg dozda uygulanan testbileşiklerinin antinosiseptif etkileri kuyruk sıkıştırma, sıcak plaka ve asetikasid ile indüklenen kıvranma testleri ile araştırılmıştır. Bileşiklerinanksiyolitik-benzeri etkilerini incelemek için delikli tahta ve yükseltilmişartı labirent testleri gerçekleştirilmiştir. Farelerin motor koordinasyonlarınıdeğerlendirmek üzere Rota-rod cihazı kullanılmıştır. Deneyler sonucunda 3f, 3gve 3h kodlu bileşiklerin kuyruk sıkıştırma ve sıcak plaka testlerindehayvanların reaksiyon sürelerini artırdığı ve 3e kodlu bileşiğin ise asetikasid ile indüklenen kıvranma testinde farelerin kıvranma sayılarını azalttığıbelirlenmiştir. Diğer yandan, 3f, 3g ve 3h kodlu bileşikler delikli tahtatestinde farelerin ilk baş daldırma sürelerini kısaltırken toplam baş daldırmasayılarını artırmıştır. Yükseltilmiş artı labirent testinde ise aynı türevlerinfarelerin açık kola giriş sayılarının ve açık kolda kalma sürelerinin yüzdelerini artırdığı ortaya konulmuştur. Rota-rod testlerinde test bileşikleri farelerindönen milden düşme sürelerini değiştirmemiştir. Tüm bu bulgular, 3f, 3g ve3h kodlu bileşiklerin santral antinosiseptif ve anksiyolitik-benzeri etkigösterdiklerine; 3e kodlu bileşiğin ise periferal antinosiseptif etkigösterdiğine işaret etmektedir., Theaim of this study was to examine the antinociceptive and anxiolytic-likeeffects of some compounds carrying benzothiazole ring. The antinociceptiveeffects of test compounds, administrated at a dose of 40 mg/kg, wereinvestigated by tail clip, hot plate and acetic acid-induced writhing tests.Hole board and elevated plus maze tests were performed to evaluate theanxiolytic-like effects of the compounds. Rota-rod device was used to assessthe motor coordinations of mice. As a result of the experiments, it wasdetermined that compounds 3f, 3g and 3h increased the reaction times of animalsin the tail clip and hot plate tests, and compound 3e reduced the writhingnumber of mice in the acetic acid-induced writhing test. On the other hand, inthe hole board test, compounds 3f, 3g and 3h reduced the first head-dippinglatencies of mice while increasing the total number of head-dips. In the elevated plus maze test, ithas been shown that the same derivatives increase the percentages of open armentries and time spent in the open arms. In the Rota-rod tests, test compoundsdid not change the falling time of mice from the rotating mill. All these findingspoint out that compounds 3f, 3g and 3h exhibit central antinociceptive andanxiolytic-like effects and compound 3e shows a peripheral antinociceptiveeffect.

Background Achyranthes Aspera Linn., known as Chirchira (Hindi), Agadha (Marathi) is an indigenous herb found in India. The herb has been reported to have variety of activities like antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic and cardiotonic, analgesic, anti-inflammatory, hypnotic, antifungal and antibacterial activity. It has been also reported to have central anti-nociceptive activity in thermal induced pain methods in our earlier studies. We wanted to study its neuropharmacological effects, which may throw light on understanding the underlying mechanism for its central activity. Purpose The present study was designed to evaluate CNS depressant and behavioral effects of A. Aspera extract and to study the phytochemical responsible for these activities with possible mode of action. Methods The effects on behavioral activity was studied using open field test (OFT). The extract was given intraperitoneally at a dose of 400 mg/kg. Diazepam (2mg/kg body weight i.p.) was used as standard. Data was analyzed by ANOVA test followed by Dunnett’s test. All the results were expressed as Mean (±SEM). P

We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (WT) mice. To understand the interaction between the cerebellum and the striatal direct and indirect pathways, we examined the expression patterns of immediate early genes (IEG) in the cerebellum of these three genotypes of mice. In the WT naive mice, there was little IEG expression. However, we observed a robust expression of c-fos mRNA in the vermis and hemisphere after running rota-rod tasks. In the vermis, c-fos was expressed throughout the lobules except lobule 7, and also in crus 1 of the ansiform lobule (Crus1), copula of the pyramis (Cop) and most significantly in the flocculus in the hemisphere. jun-B was much less expressed but more preferentially expressed in Purkinje cells. In addition, we observed significant levels of c-fos and jun-B expressions after handling mice, and after the stationary rota-rod task in naive mice. Surprisingly, we observed significant expression of c-fos and jun-B even 30 min after single weighing. Nonetheless, certain additional c-fos and jun-B expressions were observed in three genotypes of the mice that experienced several sessions of motor tasks 24 h after stationary rota-rod task and on days 1 and 5 after rota-rod tasks, but no significant differences in expressions after the running rota-rod tasks were observed among the three genotypes. In addition, there may be some differences 24 h after the stationary rota-rod task between the naive mice and the mice that experienced several sessions of motor tasks.

Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive five days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT and mutant mice.

WOS: 000299691000013, PubMed ID: 21462070, This study was designed to investigate possible antidepressant-like effects of the extract prepared from the flowers of Hypericum montbretti Spach. (Guttiferae, Clusiaceae). Phytochemical constituents of the methanolic extract were analysed by HPLC method. The main flavonoid component was detected as rutin, and another highly concentrated phenolic compound was quercitrin. Antidepressant activity of the extract was examined by tail suspension and modified forced swimming tests, whereas the motor coordination of the animals was tested by the Rota-Rod apparatus. Reboxetine at a dose of 20 mg kg(-1) was used as a reference drug. Dose-dependent antidepressant activity was observed in both tests following the administration of extract at 100 and 250 mg kg(-1) doses. To the best of our knowledge, this is the first study reporting the antidepressant activity of H. montbretti extract. Additionally, the results of this work support previous papers reporting the antidepressant activity of rutin.

WOS: 000266030800031, PubMed ID: 18922604, In the present study, some pyrazoline derivatives were synthesized to investigate their potential antinociceptive activities. 1-[(Benzoxazole/benzimidazole-2-yl)thioacetyl]pyrazoline derivatives were obtained by reacting 3,5-diaryl-1-(2-chloroacetyl)pyrazolines with 2-marcaptobenzoxazole/benzimidazole. The chemical structures of the compounds were elucidated by IR, H-1 NMR and FAB(+)-MS spectral data and Elemental Analyses. All of the compounds (100 mg/kg) exhibited significant antinociceptive activities in both hot plate and acetic acid-induced writhing tests. Naloxone (5 mg/kg) pre-treatment reversed the antinociceptive activities suggesting the involvement of opioid system in the analgesic actions. None of the compounds impaired motor coordination of animals when assessed in the Rota-Rod model. These results support the previous papers reporting the opioid sensitive antinociceptive activities of various benzoxazole/benzimidazole-pyrazoline derivative compounds

Background: Achyranthes aspera Linn., an indigenous herb, has been reported to have antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic, cardiotonic, analgesic anti-inflammatory, hypnotic, antifungal, antibacterial, and central antinociceptive activities. Aims: This study was designed to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of A. aspera (EEAA) and to find the phytochemical responsible for these activities. Materials and Methods: The pharmacological assays used to study CNS depressant effect in albino mice were rota rod and actophotometer performance test. Effects on behavioral activity were studied using open field test. The extract was given intraperitoneally (i.p.) at a dose of 400 mg/kg. Diazepam (2 mg/kg body weight i.p.) was used as standard. Statistical Analysis Used: Data were analyzed by using analysis of variance followed by Dunnett's test. P < 0.05 was considered significant. Results: Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine), and steroids as major constituents. The result of this study reflected that EEAA (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation, and showed anxiolytic activity. Conclusions: EEAA exhibit CNS depressant and significant anxiolytic activity comparable to diazepam.

Istražena su radioprotektivna kao i neka druga farmakološka svojstva WR-2721 (gamafosa)