RESUMO
Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.
Assuntos
Envelhecimento , Fluoxetina/farmacologia , Lactação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Caracteres Sexuais , Tonsila do Cerebelo/metabolismo , Animais , Feminino , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismoAssuntos
Animais , Humanos , Pesquisa Biomédica , Transtornos Mentais , Doenças do Sistema Nervoso , Neurociências , Brasil , Comunicação Interdisciplinar , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Modelos Animais , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Neurociências/tendências , Desenvolvimento de ProgramasAssuntos
Pesquisa Biomédica , Transtornos Mentais , Doenças do Sistema Nervoso , Neurociências , Animais , Brasil , Humanos , Comunicação Interdisciplinar , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Modelos Animais , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Neurociências/tendências , Desenvolvimento de ProgramasRESUMO
Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical defects in both dams and pups. The present study evaluated male rats prenatally treated with LPS for behavioral and neurological effects related to the olfactory system, which is the main sensorial path in rodents. Pregnant Wistar rats received 100 µg/kg of LPS intraperitoneally (i.p.) on gestational day (GD) 9.5, and maternal behavior was evaluated. Pups were evaluated for (1) maternal odor preference, (2) aversion to cat odor, (3) monoamine levels and turnover in the olfactory bulb (OB) and (4) protein expression (via immunoblotting) within the OB dopaminergic system and glial cells. Results showed that prenatal LPS exposure impaired maternal preference and cat odor aversion and decreased dopamine (DA) levels in the OB. This dopaminergic impairment may have been due to defects in another brain area given that protein expression of the first enzyme in the DA biosynthetic pathway was unchanged in the OB. Moreover, there was no change in the protein expression of the DA receptors. The fact that the number of astrocytes and microglia was not increased suggests that prenatal LPS did not induce neuroinflammation in the OB. Furthermore, given that maternal care was not impaired, abnormalities in the offspring were not the result of reduced maternal care.