Environmental factors such as maternal diet, determine the pathologies that appear early in life and can persist in adulthood. Maternally modified diets provided through pregnancy and lactation increase the predisposition of offspring to the development of many diseases, including obesity, diabetes, and neurodevelopmental and mental disorders such as depression. Fetal and early postnatal development are sensitive periods in the offspring’s life in which maternal nutrition influences epigenetic modifications, which results in changes in gene expression and affects molecular phenotype. This study aimed to evaluate the impact of maternal modified types of diet, including a high-fat diet (HFD), high-carbohydrate diet (HCD) and mixed diet (MD) during pregnancy and lactation on phenotypic changes in rat offspring with respect to anhedonia, depressive- and anxiety-like behavior, memory impairment, and gene expression profile in the frontal cortex. Behavioral results indicate that maternal HFD provokes depressive-like behavior and molecular findings showed that HFD leads to persistent transcriptomics alterations. Moreover, a HFD significantly influences the expression of neuronal markers specific to excitatory and inhibitory cortical neurons. Collectively, these experiments highlight the complexity of the impact of maternal modified diet during fetal programming. Undoubtedly, maternal HFD affects brain development and our findings suggest that nutrition exerts significant changes in brain function that may be associated with depression.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.