Dexamethasone suppresses the locomotor response of neonatal rats to novel environment

•In saline-treated pups, locomotor response to novelty observed since postnatal day 5.•Dexamethasone suppresses the pups’ locomotor response to novel environment.•Dexamethasone suppresses the locomotor response of rat pups to low temperature.•Dexamethasone upregulates the level of active caspase-3 in the prefrontal cortex. Locomotion of animals in the novel environment is determined by two main factors—the intrinsic motor activity and the specific locomotor response to novelty. Glucocorticoids alter neurobehavioral development of mammals and its locomotor manifestations. However, it remains unclear whether the intrinsic and/or the novelty-induced activity are affected by glucocorticoids during early life. Here, the principal component analysis was used to determine the main factors that underlie alterations in locomotion of rat pups treated with dexamethasone. It was shown that neonatal rats exhibited an enhanced locomotion in the novel environment beginning from postnatal day (PD) 5. We found for the first time that this reaction was significantly suppressed by dexamethasone. The effect was specific to the novelty-induced component of behavior, while the intrinsic locomotor activity was not affected by glucocorticoid treatment. The suppression of the behavioral response to novelty was maximal at PD7 and vanquished at PD10–11. In parallel with the hormonal effect on the behavior, dexamethasone upregulated the main cell death executor—active caspase-3 in the prefrontal cortex of 7-day old rats. Thus, dexamethasone-induced alterations in the novelty-related behavior may be the earliest visible signs of the brain damage that could lead to forthcoming depressive state or schizophrenia, emerging as a result of neonatal stress or glucocorticoid treatment.