The present study provides evidence for the hypothesis that the extent and the direction of experience-induced synaptic changes in cortical areas correlates with time windows of neuronal as well as endocrine development. Repeated brief exposure to maternal separation prior to the stress hyporesponsive period (SHRP) of the hypothalamic-pituitary-adrenal (HPA) axis induced significantly reduced dendritic spine density (-16%) in layer II/III pyramidal neurons of the anterior cingulate cortex (ACd) of 21-day-old rats, whereas separation after termination of the SHRP resulted in increased spine densities (+16%) in this neuron type. In addition, rats of both groups displayed elevated basal plasma levels of corticosterone at this age. Separation during the SHRP (postnatal days 5-7) did not influence spine density in the ACd, and basal corticosterone levels remained unchanged. In contrast, pyramidal neurons in the somatosensory cortex (SSC) displayed significantly enhanced spine densities (up to 52% increase) independent from the time of separation. These results indicate that alterations in the synaptic balance in limbic and sensory cortical regions in response to early emotional experience are region-specific and related to the maturational stage of endocrine and neuronal systems.