Among all mammalian species, pups are the most highly dependent on their mothers not only for nutrition but also for physical interaction. Therefore, disruption of the mother–pup interaction changes the physiology and behavior of pups. We reviewed the experimental procedure of early weaning, which brings about changes in the behavior and neuronal systems of the offspring of rats and mice. Thus far, we have demonstrated that early weaning results in a persistent increase in anxiety-like and aggressive behavior in adult mice. Early weaned mice also showed higher hypothalamic-pituitary-adrenal activity in response to novelty stress. Neurochemically, early weaned male mice, but not female mice, showed precocious myelination in the amygdala, decreased brain-derived neurotrophic factor protein levels in the hippocampus and prefrontal cortex, and reduced bromodeoxyuridine immunoreactivity in the dentate gyrus. These results are similar to those of human psychological disorders, and suggest that deprivation of the mother–infant interaction during the late lactation period in mice and rats provides an interesting animal model to understand the neuromolecular basis of and psychopharmacological treatments for human psychological disorders related to anxiety and higher emotionality.