Introdu??o: A fragmenta??o no cuidado maternal provocada por eventos estressores durante o in?cio da vida pode provocar o desenvolvimento de psicopatologias e preju?zos cognitivos a longo prazo. Entretanto os mecanismos neurobiol?gicos que possivelmente mediam estas altera??es n?o foram completamente elucidados. Ainda mais, modelos pr?-cl?nicos cl?ssicos de estresse precoce (ELS) vem produzindo resultados inconclusivos e com baixos n?veis de replicabilidade. Objetivos: O objetivo do estudo 1 foi atrav?s de uma revis?o sistem?tica investigar o impacto de m?ltiplos modelos de ELS sobre o comportamento maternal de ratos e camundongos. O estudo 2 se prop?s a investigar o impacto da exposi??o a um modelo combinado de ELS sobre o comportamento do tipo ansioso e marcadores centrais e perif?ricos de funcionamento do eixo hipot?lamo-pituit?ria-adrenal (HPA). O estudo 3 investigou o impacto do modelo combinado de ELS sobre tarefas de mem?ria dependentes do funcionamento do c?rtex pr?-frontal (PFC) e a sua rela??o com a express?o de receptores dopamin?rgicos na mesma regi?o. M?todos: A estrat?gia de busca para realiza??o da revis?o sistem?tica (estudo 1) foi realizada utilizando tr?s bases de dados: PUBMED, Embase e Web of Science. Em todas as an?lises o grupo ELS foi comparado somente ao grupo controle. Os desfechos foram categorizados em oito comportamentos maternais. Al?m disso, a qualidade metodol?gica dos estudos foi avaliada. Para realiza??o do estudo 2, camundongos machos da linhagem BALB/cJ foram expostos a um modelo de ELS que combina Separa??o materna (SM) e Limited Bedding (LB) do dia p?s-natal 2 ao 15. Durante a primeira semana de desenvolvimento o comportamento maternal foi avaliado. No final da adolesc?ncia os animais foram testados no Open Field (OF), Elevated Plus Maze (EPM) e Light/Dark (LD). Ap?s os testes comportamentais, os animais foram sacrificados, e os n?veis de mRNA do receptor de glicocorticoide (Nr3c1), horm?nio liberador de corticotrofina (Crh) e seu receptor do tipo 1 (Crhr1) foram medidos no hipot?lamo. Al?m disso, os n?veis de corticosterona plasm?tica foram analisados. No estudo 3, machos e f?meas da linhagem BALB/cJ foram expostos ao mesmo modelo combinado de estresse precoce (SM + LB). O comportamento materno pr?-SM e p?s-SM foi avaliado durante as 2 primeiras semanas do desenvolvimento. Na adolesc?ncia, camundongos machos e f?meas foram testados nas tarefas de mem?ria Y-maze e Object in Place (OIP). Ap?s os testes cognitivos, os animais foram sacrificados e a express?o de mRNA do receptor de dopamina D1 (Drd1), Drd2 e Drd3 foi medida no c?rtex pr?-frontal medial (mPFC) por qPCR em tempo real. Resultados: No estudo 1 foi identificado que a exposi??o a SM aumenta o comportamento maternal ap?s o protocolo de estresse, resultado que ficou mais evidente em estudos com ratos. Em rela??o ao modelo de LB, foi observado um aumento na fragmenta??o do cuidado maternal, especialmente em estudos com camundongos. O estudo 2 reportou que as m?es apresentaram uma piora na qualidade do comportamento maternal e um aumento no n?mero de sa?das do ninho. Na adolesc?ncia os animais do grupo ELS apresentaram um aumento no comportamento do tipo ansioso no OF, EPM e LD. Em rela??o aos marcadores biol?gicos, foi observado um aumento nos n?veis de Crh no hipot?lamo dos animais estressados. Ainda mais, os animais do grupo ELS apresentaram uma diminui??o nos n?veis de corticosterona plasm?tica. O estudo 3 identificou que o modelo de ELS aumenta o comportamento materno somente ap?s a SM. Nos testes cognitivos, machos e f?meas expostos ao modelo combinado de ELS apresentaram preju?zos no Y-maze e OIP. Em rela??o a n?veis de mRNA no mPFC, os tr?s genes investigados (Drd1, Drd2 e Drd3) tiveram sua express?o diminu?da independente de sexo ap?s a exposi??o ao modelo de ELS. Conclus?es: Em conclus?o, foi observado que a exposi??o ao ELS provoca altera??es no cuidado maternal que podem estar relacionadas com o desenvolvimento de psicopatologias e preju?zos cognitivos ao longo da vida. Mais tarde na vida, os animais expostos ao modelo proposto de SM + LB apresentaram aumento no comportamento do tipo ansioso e modifica??es centrais e perif?ricas no funcionamento do eixo HPA. Por fim, a exposi??o ao modelo combinado de ELS tamb?m provocou preju?zos em tarefas dependentes do PFC em ambos os sexos. Estes preju?zos podem ser em parte associados a altera??o na express?o dos receptores de dopamina, em especial o Drd1. Introduction: Fragmentation in maternal care provoked by stressful events during early life can lead to the development of psychopathologies and long-term cognitive impairments. However, the neurobiological mechanisms that possibly mediate these alterations have not been fully elucidated. Furthermore, classic preclinical models of early stress (ELS) have been reporting inconclusive results with low levels of replicability. Objectives: The objective of study 1 was to perform a systematic review in order to investigate the impact of multiple models of ELS on the maternal behavior of rats and mice. Study 2 aimed to investigate the impact of exposure to a combined model of ELS on anxiety-like behavior, as well as central and peripheral markers of hypothalamic-pituitary-adrenal (HPA) functioning. Study 3 investigated the impact of the combined ELS model on prefrontal cortex (PFC) dependent memory tasks and its relationship with the expression of dopaminergic receptors in the same region. Methods: The search strategy used in the systematic review (study 1) was carried out using three databases: PUBMED, Embase and Web of Science. In all analyzes, the ELS was compared only to the control group. Outcomes were categorized into eight maternal behaviors. The methodological quality of the studies was also evaluated. For study 2, male BALB/cJ mice were exposed to an ELS model that combines Maternal Separation (SM) with Limited Bedding (LB) from postnatal day 2 to 15. During the first week of development, the maternal behavior was assessed. At late adolescence the animals were tested in the Open Field (OF), Elevated Plus Maze (EPM) and Light/Dark (LD). After the behavioral tests, the animals were sacrificed, and the mRNA levels of glucocorticoid receptor (Nr3c1), corticotrophin-releasing hormone (Crh), and its type 1 receptor (Crhr1) were measured in the hypothalamus. In addition, plasmatic corticosterone levels were analyzed. In study 3, BALB/cJ males and females were exposed to the same combined model of early stress (SM + LB). Maternal behavior pre-SM and post-SM was assessed during the first 2 weeks of development. During adolescence, male and female mice were tested in the Y-maze and Object in Place (OIP) memory tasks. After behavioral tests, the animals were sacrificed and the mRNA levels of dopamine receptor D1 (Drd1), Drd2, and Drd3 were measured in the medial prefrontal cortex (mPFC) by Real-time qPCR. Results: In study 1, it was identified that MS exposure increases maternal behavior after post-MS, and this result was more evident in studies with rats. Regarding the LB model, an increase in the fragmentation of maternal care was observed, especially in studies with mice. Study 2 reported that mothers showed a worsening in the quality of maternal behavior and an increase in the number of exits from the nest. During adolescence, the animals of the ELS group showed an increased anxiety-like behavior in the OF, EPM and LD. Regarding biological markers, an increase in Crh levels was observed in the hypothalamus of stressed animals. Furthermore, the animals in the ELS group showed a decrease in plasmatic corticosterone levels. Study 3 identified that the ELS model increases maternal behavior only post-MS. In the cognitive tests, males and females exposed to the combined ELS model performed worse in the Y-maze and OIP. Regarding mRNA levels in the mPFC, the three genes investigated (Drd1, Drd2 and Drd3) had their expression decreased regardless of sex after exposure to the ELS model. Conclusion: In conclusion, it was observed that ELS exposure promotes maternal behavior alterations that may be related to the development of psychopathologies and cognitive impairments throughout life. Later in life, animals exposed to the proposed SM + LB model showed an increase in anxiety-like behavior, as well as central and peripheral changes in HPA axis functioning. Finally, exposure to the combined ELS model also caused impairments in PFC-dependent tasks in both sexes. Those impairments can be partly associated with changes in the expression of dopamine receptors, especially Drd1. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES