Permanent changes in novelty-induced arousal and behavioral depression were studied in adult male Wistar rats having received sc injections of 1 μg/g body wt dexamethasone (DEX) or ACTH-(4-9) analogue (ORG 2766), or the combined treatment of these substances at Postnatal Days 1, 3, and 5. Treatment with DEX increased immobility in the Porsolt's water immersion and closed-field tests, delayed start latency, and attenuated orientation motility in an open-field, and enhanced defensive burying activity. On the contrary, the ACTH peptide caused more active behavior, resulted in an increased molility in the Porsolt's test, and decreased immobility in the closed-field chamber compared to controls. Behavioral reactivity of rats after combined DEX and ACTH peptide treatments was comparable to that of saline controls. The hormone treatments did not alter basal and stress-induced circulating corticosterone levels assessed at the adult age. The data suggest that neonatal DEX strengthens the development of brain mechanisms supporting behavioral depression in response to stressful situations, while ORG 2766 has principally an opposite effect and is able to compensate the longterm aberrant behavioral effects of neonatal DEX treatment. © 1993 by Academic Press, Inc.