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1.
Toxicol Appl Pharmacol ; 483: 116805, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38191078

RESUMO

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.


Assuntos
Fluoxetina , Lactação , Humanos , Feminino , Criança , Ratos , Animais , Adulto , Fluoxetina/toxicidade , Leite Humano , Antidepressivos/farmacologia , Peso Corporal
2.
Toxicol Appl Pharmacol ; 483: 116819, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38215996

RESUMO

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.


Assuntos
Atrazina , Herbicidas , Praguicidas , Feminino , Ratos , Animais , Masculino , Atrazina/toxicidade , Herbicidas/toxicidade , Encéfalo , Dopamina
3.
Behav Brain Res ; 459: 114799, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38065224

RESUMO

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.


Assuntos
Depressão Pós-Parto , Transtorno Depressivo Maior , Ketamina , Humanos , Criança , Ratos , Masculino , Animais , Feminino , Depressão Pós-Parto/tratamento farmacológico , Lactação , Privação Materna , Depressão/tratamento farmacológico , Antidepressivos , Transtorno Depressivo Maior/tratamento farmacológico
4.
Behav Brain Res ; 436: 114082, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36041571

RESUMO

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.


Assuntos
Depressão Pós-Parto , Animais , Corticosterona , Modelos Animais de Doenças , Feminino , Lactação , Privação Materna , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/etiologia , Tireotropina
5.
Behav Brain Res ; 377: 112246, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31539576

RESUMO

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.


Assuntos
Comportamento Animal/efeitos dos fármacos , Fluoxetina/farmacologia , Lactação , Comportamento Materno/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Comportamento Social , Fatores Etários , Animais , Animais Lactentes , Feminino , Fluoxetina/administração & dosagem , Humanos , Masculino , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem
6.
Pharmacol Rep ; 72(1): 24-35, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016837

RESUMO

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.


Assuntos
Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Animais , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Depressão/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ketamina/farmacologia , Ketamina/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Testes de Toxicidade
7.
Behav Brain Res ; 359: 958-966, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29913187

RESUMO

Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice.


Assuntos
Proteínas de Membrana/genética , Mutação/genética , Neurotransmissores/metabolismo , Membrana dos Otólitos/patologia , Doenças Vestibulares/genética , Animais , Comportamento Exploratório/fisiologia , Elevação dos Membros Posteriores , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Atividade Motora , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , Aprendizagem Espacial , Natação , Doenças Vestibulares/etiologia
8.
Pharmacol Biochem Behav ; 181: 1-8, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30946884

RESUMO

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.


Assuntos
Ansiedade/induzido quimicamente , Memória/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Neurônios Serotoninérgicos/efeitos dos fármacos , Vareniclina/farmacologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Modelos Animais , Atividade Motora/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Agonistas Nicotínicos/administração & dosagem , Ratos , Ratos Wistar , Serotonina/metabolismo , Fumar/tratamento farmacológico , Abandono do Hábito de Fumar/métodos , Vareniclina/administração & dosagem , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Ácido gama-Aminobutírico/metabolismo
9.
Basic Clin Pharmacol Toxicol ; 122(3): 305-309, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28944993

RESUMO

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.


Assuntos
Agonistas Nicotínicos/efeitos adversos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Vareniclina/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Coração/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Agonistas Nicotínicos/administração & dosagem , Especificidade de Órgãos , Ratos Wistar , Reprodutibilidade dos Testes , Testes de Toxicidade Subaguda , Vareniclina/administração & dosagem , Aumento de Peso/efeitos dos fármacos
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