Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

Peripubertal exposure of atrazine cause decrease in exploratory activity, deficits in sociability and few alterations on brain monoaminergic systems of rats.

Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.

Ketamine causes poor maternal care in rats with postpartum depression and leads to few behavioral and neurochemical alterations on male offspring.

Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2-12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2-21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.

Postpartum depression in rats causes poor maternal care and neurochemical alterations on dams and long-lasting impairment in sociability on the offspring.

Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.

Development, Optimization, and Validation of Forensic Analytical Method for Quantification of Anticholinesterase Pesticides in Biological Matrices from Suspected Cases of Animal Poisoning.

Anticholinesterase pesticides are a main cause of the intentional or accidental poisoning of animals. Anticholinesterases include several substances that cause the overstimulation of both central and peripheral acetylcholine-dependent neurotransmission. Forensic analyses of poisoning cases require high levels of expertise, are costly, and often do not provide reliable quantitative information for unambiguous conclusions. The purpose of the present study was to develop and validate a method of high-performance liquid chromatography with diode array detector (HPLC−DAD) for the identification and quantitation of n-methyl carbamates, organophosphates and respective metabolites from biological samples of animals that were suspected of poisoning. HPLC−DAD is reliable, fast, simplistic and cost-effective. The method was validated for biological samples obtained from stomach contents, liver, vitreous humor and blood from four different animal species. The validation of the method was achieved using the following analytical parameters: linearity, precision, accuracy, selectivity, recovery, and matrix effect. The method showed linearity at the range of 25−500 µg/mL, and the correlation coefficient (r2) values were >0.99 for all matrices. Precision and accuracy were determined by the (a) coefficient of variation (CV), (b) relative standard deviation low-quality control (LQC), (c) medium-quality control (QCM), and (d) high-quality control (QCA). The indicated parameters were all less than 15%. The recovery of analytes ranged from 31 to 71%. The analysis of results showed no significant interfering peaks due to common xenobiotics or matrix effects. The abovementioned method was used to positively identify pesticide analytes in 44 of the 51 animal samples that were suspected of poisoning, demonstrating its usefulness as a forensic tool.

Post-Partum Depression Lactating Rat Model for Evaluating Ketamine's Safety as a Pharmacotherapeutic Treatment: Roles in Cardiac and Urinary Function.

Depression is one of the world's most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother-child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine's clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother-infant bond early in the offspring's life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals' cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.

Exposure of dams to fluoxetine during lactation disturbs maternal behavior but had no effect on the offspring behavior.

Fluoxetine is one of the most commonly prescribed drugs for treatment of depression during pregnancy as well as postpartum. Nevertheless, fluoxetine can cross the placental barrier and/or be secreted through breastmilk and questions remain unanswered regarding safety of the unborn and/or nursing infant. Passive administration of antidepressants to infants can cause neurological developmental delay and/or dysfunction. To date, there are limited studies on neurobehavioral effects due to passive administration of fluoxetine in nursing animals. Thus, the aim of the present study was to evaluate the effects of fluoxetine exposure on the behavior of lactating dams and their offspring. Dams received either 1, 10 or 20 mg/kg fluoxetine via oral gavage (controls received water alone) from lactating day (LD) 1 to 21. Maternal behavioral studies were conducted from LD5 to LD7 and offspring studies were conducted from LD2 to LD60. Results showed dysfunction in maternal behavior, both in direct and indirect behavior, but there were no differences and/or deficiencies observed in offspring behavior. These data suggest that the impairment of dams maternal behavior combined with the amount of fluoxetine that the offspring received through breast milk during lactation did not alter their social behavior in infancy and/or adulthood, suggesting no neurodevelopmental damage associated with maternal use of fluoxetine. This study contributes to the field of human psychiatric diseases by further elucidating the effects of antidepressant medications on the health of mothers as well as children who were passively exposed to drug treatment.

Preclinical toxicological study of prolonged exposure to ketamine as an antidepressant.

BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.

Prolonged exposure of rats to varenicline increases anxiety and alters serotonergic system, but has no effect on memory.

Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors. Recent clinical trial data support use of varenicline for treatment of conditions/addictions that are not related to smoking cessation. Considering the importance of this issue and the need for new studies on its effects, especially on behavior, more studies using animal models are necessary. Thus, the aim of this study was to evaluate the effects of prolonged exposure to varenicline in anxiety-like behavior and memory, as well as in cerebral neurochemistry of rats. Male rats received three different doses of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg orally (gavage) for 30 days. Animal behavior was analyzed through open field, elevated plus maze, light/dark box, social interaction, Barnes maze and novel object recognition tests. Neurotransmitter levels and their metabolites in different brain structures (hippocampus, striatum and frontal cortex) were measured. Results showed that prolonged exposure of rats to varenicline: 1) did not interfere in motor activity, but caused an anxiogenic effect on elevated plus maze, light/dark box and social interaction testes; 2) did not alter memory; and 3) promoted alterations on serotoninergic system in the striatum and frontal cortex. In conclusion, compilation of the data indicates that prolonged exposure of rats to varenicline promoted anxiogenic effects and alteration in serotonergic system, which corroborated behavioral findings.

Evaluation of Prolonged Exposure to Varenicline in Adult Rats: Haematological, Biochemical and Anatomopathological Studies.

Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4ß2 and α3ß4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.

Perinatal exposure to an aromatase inhibitor glyphosate-base herbicide reduced male and female social behavior in juvenile age and the sexual behavior at adult female rats / Exposição perinatal ao inibidor da aromatase a base de glifosato reduz o comportamento social de machos e fêmeas e o comportamento sexual de ratas

Objectives: The herbicide glyphosate, a pesticide used in agriculture to control weeds, both in food crops and in other agricultural areas, has been identified as an endocrine modulator through the inhibition of aromatase activity and the activation of estrogen receptors. The present study examined the effects of a glyphosate-based herbicide (Roundup® (GLY-BH) on sexual dimorphism of rats after perinatal exposure to low and high GLY-BH in males and females offspring. Methods: Two groups of pregnant rats were treated with two doses of GLY-BH (50 or 150 mg/kg) from day 15 of gestation (GD15) to postnatal day 7 (PND7). Play fighting behavior was observed at the juvenile stage and during social and sexual behaviors in adulthood. Results: Perinatal GLY-BH exposure reduced male and female body weight at 28, 75, and 90 days of age. The play fighting behavior was decreased in both sexes, but female rats were more affected. The sexual behaviors were reduced only in females. Conclusions: Perinatal exposure to both doses of GLY-BH promoted sexually dimorphic effects in both juvenile and adulthood stages. These effects were attributed to the inhibition of aromatase activity induced by exposure to GLY-BH in the perinatal period.(AU)

Objetivos: O glifosato é um herbicida não seletivo, usado em muitas culturas alimentares e não alimentares e em áreas não agrícolas, sendo que os produtos a base de glifosato atuam como moduladores das funções endócrinas por meio da inibição da atividade da aromatase e da ativação de receptores de estrógeno. O presente estudo avaliou os efeitos do herbicida Roundup® (GLY-BH) à base de glifosato, em comportamentos sexualmente dimórficos de ratos após exposição perinatal a doses baixas e altas de GLY-BH no período perinatal. Métodos: Ratas prenhas foram tratadas com 50 ou 150 mg/kg de GLY-BH do 15º dia de gestação (GD15) ao 7º dia de lactação (LD7). O comportamento de luta/brincar foi observado na fase juvenil e os comportamentos social e sexual na idade adulta. Resultados: a exposição perinatal a GLY-BH reduziu o peso corporal de machos e fêmeas aos 28, 75 e 90 dias de idade. O comportamento de luta/brincar diminuiu em ambos os sexos, sendo as ratas foram as mais afetadas. O comportamento sexual foi reduzido apenas nas fêmeas. Conclusões: A exposição perinatal a ambas as doses do GLY- BH promoveu tanto na idade juvenil como na idade adulta, efeitos sexualmente dimórficos. Esses efeitos foram atribuídos à inibição da atividade da aromatase induzida exposição perinatal ao GLY-BH.(AU)

Type 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like Behavior in Male Mice.

Millions of levothyroxine-treated hypothyroid patients complain of impaired cognition despite normal TSH serum levels. This could reflect abnormalities in the type 2 deiodinase (D2)-mediated T4-to-T3 conversion, given their much greater dependence on the D2 pathway for T3 production. T3 normally reaches the brain directly from the circulation or is produced locally by D2 in astrocytes. Here we report that mice with astrocyte-specific Dio2 inactivation (Astro-D2KO) have normal serum T3 but exhibit anxiety-depression-like behavior as found in open field and elevated plus maze studies and when tested for depression using the tail-suspension and the forced-swimming tests. Remarkably, 4 weeks of daily treadmill exercise sessions eliminated this phenotype. Microarray gene expression profiling of the Astro-D2KO hippocampi identified an enrichment of three gene sets related to inflammation and impoverishment of three gene sets related to mitochondrial function and response to oxidative stress. Despite normal neurogenesis, the Astro-D2KO hippocampi exhibited decreased expression of four of six known to be positively regulated genes by T3, ie, Mbp (∼43%), Mag (∼34%), Hr (∼49%), and Aldh1a1 (∼61%) and increased expression of 3 of 12 genes negatively regulated by T3, ie, Dgkg (∼17%), Syce2 (∼26%), and Col6a1 (∼3-fold) by quantitative real-time PCR. Notably, in Astro-D2KO animals, there was also a reduction in mRNA levels of genes known to be affected in classical animal models of depression, ie, Bdnf (∼18%), Ntf3 (∼43%), Nmdar (∼26%), and GR (∼20%), which were also normalized by daily exercise sessions. These findings suggest that defects in Dio2 expression in the brain could result in mood and behavioral disorders.

Effects of exposure to glyphosate in male and female mice behavior in pubertal period / Efeitos comportamentais da esposição na piberdade de camundongos machos e fêmeas ao glifosato

The present study aims to investigate the effects of pre-pubertal exposure of male and female mice to a commercial formulation of glyphosate on sexual dimorphism observed in animal models of emotionality, anxiety and depression. For this, mice were exposed from 23 days of age (PND) until PND 45 to glyphosate (50 mg/kg, per os) or saline solution, and, ten days after the end of treatments, male and female mice were observed in the open field (OF), elevated plus maze (EPM) or forced swimming test (FWT). Results showed that exposure to glyphosate: 1) reduced the locomotion frequency of male mice similarly to female mice in the OF and female mice had an increase in rearing behavior and in the immobility time; 2) reduced in male mice the motor activity both in the OF and EPM, while no effects were observed in female mice; 3) in the SWT male mice had a decreased time of float similarly female mice. We concluded that pre-pubertal exposure to glyphosate reduced in male mice the capacity of exploration in the OF and EPM tests suggesting that the herbicide interfered with the central mechanism related to brain masculinization of exploratory and anxiety behavioral models. In the FWT it was observed a decreased depressive response in male mice while in female an increased response was detected.

O presente estudo teve como objetivo investigar em camundongos machos e fêmeas o efeito da exposição a uma formulação comercial de glifosato durante o período de pré-pubere em modelos comportamentais de emocionalidade, ansiedade e depressão. Para isto, camundongos foram expostos a partir de 23 dias de idade (dia pós-natal-PND) até o PND 45 ao glifosato (50 mg/kg, via oral) ou solução salina. Dez dias após o término do tratamento, os animais, machos e fêmeas, foram observados no campo aberto (OF), labirinto em cruz elevado (EPM) ou teste de natação forçada (FWT). Os resultados mostraram que a exposição ao glifosato: 1) reduziu de forma similar a frequência de locomoção dos camundongos em ambos os sexos; 2) reduziu a atividade motora tanto no OF como no PM em camundongos machos, sem alterações observadas em fêmeas; 3) no SWT os camundongos machos apresentaram redução no tempo de flutuação similar ao das fêmeas. Concluiu-se que a exposição pré-pubere ao glifosato reduziu em machos a capacidade de exploração no OF e EPM e no tempo de flutuação no FWT sugerindo que o herbicida interferiu com mecanismos centrais relacionados com masculinização do cérebro ligados à exploração e ansiedade. No FWT observou-se menor depressão em machos e exacerbação da resposta em fêmeas.

Behavioral and neurochemical evidence of deltamethrin anxiogenic-like effects in rats / Evidências neuroquímicas e comportamentais do efeito ansiogênico da deltametrina em ratos

Pyrethroid insecticides are extensively used for pest control around the house, flea prevention for pets, and plant sprays for the home and in agriculture. Deltamethrin (DTM) is a Type II pyrethroid insecticide used to control a variety of insects in agriculture and domestic environments. The present study investigated the possible anxiogenic effects of DTM (1, 3, and 10 mg/kg) in rats using behavioral and neurochemical methods. We assessed general locomotor activity and behavior in the elevated plus maze and open field test. Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) Striatal and hippocampal neurotransmitter and metabolite levels were also measured. DTM (i) reduced locomotion and rearing frequency, (ii) slightly increased the duration of immobility, (iii) reduced the time engaged in social interaction, (iv) reduced the percentage of entries into and time spent on the open arms of the elevated plus maze, (v) reduced the number of center crossings in the elevated plus maze, (vi) increased striatal serotonin neurotransmitter and its metabolite, and (vii) did not alter motor coordination on the rotarod, grooming duration in the open field test, rectal temperature, or hippocampal neurotransmitter levels. These data suggest that DTM at the present doses and under these experimental conditions presented a similar profile to that of anxiogenic drugs, unrelated with the increased serotonin neurotransmission.

Inseticidas piretróides são amplamente utilizados para controle de pragas, como na prevenção de pulgas em animais de estimação e sprays de plantas para a casa e na agricultura. Deltametrina (DTM) é um inseticida piretróide tipo II usado para controlar uma variedade de insetos na agricultura e ambientes domésticos. O presente estudo investigou os possíveis efeitos ansiogênicos de DTM (1, 3 e 10 mg/kg) em ratos, utilizando métodos comportamentais e neuroquímicos. Foi avaliada a atividade locomotora geral e comportamento no labirinto em cruz elevado e teste de campo aberto. Os níveis de neurotransmissores e metabólitos no estriado e hipocampo também foram mensurados. DTM (i) reduziu a locomoção e a frequência de levantar, (ii) aumentou da duração da imobilidade, (iii) reduziu o tempo de interacção social, (iv) reduziu a percentagem de entradas e tempo gasto nos braços abertos do elevado labirinto em cruz, (v) reduziu o número de cruzamentos no centro do labirinto em cruz elevado, (vi) aumentou neurotransmissor serotonina e de seu metabólito estriatal, e (vii) não alterou a coordenação motora no rotarod, duração do grooming no teste de campo aberto, temperatura retal, ou níveis de neurotransmissores do hipocampo. Estes dados sugerem que DTM nas presentes doses e sob estas condições experimentais apresentaram um perfil semelhante ao de drogas ansiogénicas, não relacionados ao aumento da serotonina estriatal.

Preclinical study of an antiobesity herbal medicine, PholiaNegra (X´Tract Vetorized)TM, in male and female rats fed with high-fat diet: comparison with sibutramine / Estudo pré-clínico de um medicamento antiobesidade de ervas, PholiaNegra (X'Tract Vetorized)TM, em ratos machos e fêmeas alimentados com dieta hipercalórica: comparação com sibutramina

Objective - To assess, in this preclinical study, the effectiveness of a herbal medicine developed from a group of plants of the genus Ilexin the adjuvant treatment of obesity in rats fed with a high-fat diet. Phytotherapy is becoming increasingly popular both for the results it yields in several pathologies and because they are growing herbal medicine studies showing its effectiveness. Methods - Male and female rats were fed with a high-fat diet for one month. The diet was then replaced by a chow diet. All male and female rats received the PholiaNegra(X´Tract Vetorized)TM or water. The treatment was orally administered twice a day over 30 days. Body weight gain was assessed weekly and, at the end of treatment, the total body weight gain was calculated. A positive control with sibutramine (7.5 mg/kg, twice a day, orally, over 30 day was also included. Results - A significant reduction in weekly body weight gain, as well as in total weight gain, in both male and female rats after the herbal medicine administration. The index of body weight loss showed that PholiaNegra (X´TractVetorized)TM was more effective in reducing body weight in female than in male rats. The sibutramine treatment showed the same profile as PholiaNegra (X´Tract Vetorized)TM treatment. Conclusion - The present data indicate that PholiaNegra (X´Tract Vetorized)TM herbal medicine was effective in decreasing body weight in male and female rats submitted to a high-fat diet, and showed a similar profile to that of sibutramine.

Objetivo - Avaliar, neste estudo pré-clínico, a eficácia de um medicamento desenvolvido a partir de um grupo de plantas do gênero Ilex no tratamento adjuvante da obesidade em ratos alimentados com uma dieta hipercalórica. A fitoterapia está se tornando cada vez mais popular, tanto pelos resultados positivos em diversas doenças e porque estão crescendo estudos de medicina de ervas que mostram a sua eficácia. Métodos - Ratos machos e fêmeas foram alimentados com uma dieta rica em gordura durante um mês. A dieta foi então substituída por uma ração normal do biotério. Todos ratos e ratas foram tratado com PholiaNegra (X´Tract Vetorized)TM ou água. O tratamento foi administrado por via oral, duas vezes por dia durante 30 dias. O ganho de peso corporal foi avaliado semanalmente e, no final do tratamento, o ganho de peso total foi calculado. Como controle positivo empregou-se a sibutramina (7,5 mg/kg, duas vezes por dia, por via oral, durante 30 dias. Resultados - Observou-se redução significativa no ganho de peso corporal semanal, bem como do ganho de peso total, tanto nos ratos machos e fêmeas, após a administração do medicamento à base de plantas. O índice de perda de peso corporal mostrou que Pholia-Negra (X´Tract Vetorized)TM foi mais eficaz na redução do peso corporal nas fêmeas do que em ratos machos. O tratamento com sibutramina mostrou o mesmo perfil obtido com o tratamento com PholiaNegra (X´Tract Vetorized)TM. Conclusão - Os presentes dados indicam que PholiaNegra (X´Tract Vetorized)TM foi eficaz em diminuir o peso corporal em ratos machos e fêmeas submetidos a uma dieta rica em gordura,e mostrou um perfil semelhante ao da sibutramina.

Behavioral effects of acute glyphosate exposure in male and female Balb/c mice / Efeitos comportamentais da exposição aguda ao gliposato em camundongos Balb/c machos e fêmeas

We investigated the behavioral effects induced by an acute exposure to a commercial formulation of glyphosate (GF) in a dose that was about double the concentration of the no observed adverse effect level (NOAEL) in male and female BALB/c mice. The acute neurotoxicity induced by GF exposure was determined through analysis of general activity, the sensory system, the psychomotor system, the central nervous system and the autonomous nervous system in both male and female mice. The behavioral effects on exploration, anxiety and depression induced by GF exposure were determined with the open field, elevated plus maze and tail suspension tests, respectively. GF induced few signs of acute neurotoxicity. Locomotion in the open field was decreased in only female mice. No signs of anxiety were detected in the plus maze test in both sex, however, a reduced exploration was observed in male mice in this apparatus. In the tail suspension test, both male and female mice showed an increased immobility time. No interaction between sex and treatment was detected. In conclusion, GF exposure at about a dose twice that of the NOAEL induced few signs of neurotoxicity and no sexual dimorphism in all behavioral models employed.

Neste trabalho investigou-se em camundongos BALB/c, machos e fêmeas, os efeitos comportamentais da exposição aguda a uma formulação comercial do glifosato (GF) em uma dose duas vezes maior que a dose sem efeito observado (NOAEL). A neurotoxicidade aguda ao GF foi determinada por meio da análise da atividade geral, de parâmetros sensoriais, psicomotores, do sistema nervoso central e autônomo em machos e fêmeas. Os efeitos exploratório, de ansiedade e depressão induzidos pelo GF foram observados no campo aberto, labirinto em cruz elevado e no teste da suspensão da cauda, respectivamente. O GF promoveu poucos sinais de neurotoxicidade. A capacidade exploratória de fêmeas foi reduzida no campo aberto. Nenhum sinal de ansiedade foi detectado tanto em machos como em fêmeas no labirinto em cruz elevado porém, notou-se redução da exploratória neste aparelho. No teste de suspensão da cauda tanto as fêmeas como machos mostraram aumento no tempo de imobilidade. Não foi observado neste caso interação entre sexo e tratamento. Concluiu-se que a exposição ao dobro da dose da NOAEL do GF induziu poucos sinais de neurotoxicidade e poucos efeitos sexualmente dimórficos em camundongos machos e fêmeas.

Antidepressant-like effects of an apolar extract and chow enriched with Nepeta cataria (catnip) in mice

Nepeta cataria (catnip) is a plant used in pet toys and to treat human diseases. Catnip has also been used in the treatment of some depressive disorders. In this paper, we studied the antidepressant, anxiogenic, and motor activity effects of acute and repeated feeding of chow enriched with 10 percent N. cataria leaves and the acute and repeated administration of apolar and polar extracts of N. cataria leaves in male mice. The results showed that repeated feeding and acute and repeated administration with the apolar extract reduced immobility in the behavioral despair test but did not alter elevated plus maze and open-field parameters. Acute feeding and the acute and repeated administration of the polar extracts of N. cataria leaves did not alter the behavior of mice. These data suggest that N. cataria has antidepressant properties. Moreover, this antidepressant activity was present in the apolar extract

Anti-nociceptive and anti-inflammatory actions of Nepeta cataria L.var. citriodora (Becker) Balb. essential oil in mice / Efeitos antinociceptivos e anti-inflamatórios do óleo essencial de Nepeta cataria L. var. citriodora (Becker) Balb. em camundongos

Objective - Nepeta cataria (catnip) is a plant used to treat human diseases and is also found in pet toys. This study was performed to analyze the anti-nociceptive and anti-inflammatory effects of N. cataria essential oil (NCEO) in female mice. Methods - Phytochemical analyses of NCEO were performed. In addition, female mice treated with the oil were observed in an open for its general activity and to investigate the dose and time responses. The anti-nociceptive effects were evaluated by tail immersion and acetic acid writhing reflex tests.The anti-inflammatory oil properties were investigated by the carrageenan-induced edema test. Results - The results showed that 0.0005 and 0.001 mL/kg i.p. doses of NCEO increased the general activity of female mice, and the 0.0005 mL/kg dose reduced their immobility. Moreover, NCEO (0.0005 mL/kg) has anti-nociceptive properties, as the treated animals exhibited an increased latency of tail withdrawal and reduced acetic acid-induced abdominal constrictions. Furthermore, NCEO (0.0005 mL/kg) presented peripheric anti-inflammatory properties by reducing the induced edema after carrageenan injection. Conclusions - These effects may be due to the nepetalactone trans-trans and trans-cis nepetalactone isomers, which were detected as the predominant active components in the phytochemical analysis. It was suggested that the main effect of NCEO occurs on the central nervous system mechanism of pain.

Objetivo - A Nepeta cataria (catnip) é uma planta utilizada para tratar doenças humanas e também é encontrada em brinquedos de animais de estimação. O objetivo deste estudo foi analisar os efeitos antinociceptivos e anti-inflamatório do óleo essencial de N. cataria (NCEO) em camundongos fêmeas. Métodos - A análise fitoquímica do NCEO foi realizada. Além disso, os animais que foram tratados como óleo e foram observados em um campo aberto para mensurar a sua atividade em geral e investigar a dose e tempo de respostas. Os efeitos antinociceptivos foram avaliados pelos testes de imersão da cauda e reflexo de contorções abdominais causadas pelo ácido acético. As propriedades anti-inflamatórias do óleo foram investigadas pelo teste de edema induzido por carragenina. Resultados - Os resultados mostraram que 0,0005 e 0,001mL/ kg doses ip. de NCEO aumentou a atividade geral de camundongos fêmeas, e dose de 0,0005 mL/kg reduziu sua imobilidade. Além disso, NCEO (0,0005 mL/kg), tem propriedades antinociceptiva, como os animais tratados apresentaram uma maior latência de retirada de cauda e reduziu as contorções abdominais induzidas pelo ácido acético. Além disso, NCEO (0,0005mL/kg) apresentou efeito periférico e propriedades anti-inflamatórias, reduzindo o edema induzido após a injeção de carragenina. Conclusões - Estes efeitos podem ser devido aos isômeros nepetalactone trans-trans e nepetalactone trans-cis, que foram detectados como os componentes ativos predominante na análise fitoquímica. Foi sugerido que o principal efeito da NCEO ocorre no mecanismo do sistema nervoso central da dor.