Pharmacological treatment in neonatal life may have enduring effects, reducing the alterations in hormonal homeostatic programming mechanisms induced by early repeated handling. Several investigations suggest that the role of early environment in influencing development mainly involves the hypothalamic-pituitary-adrenal axis. Therefore, we are examining whether 1) daily neonatal handling, applied from birth to weaning induces HPA hormones alterations in mice lasting up to the adult age; and 2) if the administration of an antisense oligodeoxynucleotide versus pro-opiomelanocortin (As-POMC) prevents hormonal alterations observed in previously handled mice (Handled). In the adult phase (90 days), Handled are overweight and have higher basal plasma immuno-reactive (ir)-corticosterone and adrenocorticotropin (ir-ACTH), and higher pituitary ir-ACTH; while they have lower hypothalamic ir-ACTH and corticotropin-releasing hormone (ir-CRH) in comparison with the non-handled mice. As-POMC (0.05-0.1 nmol/g body weight per day) administered during the same period dose-dependently prevents the increase in body weight, in plasma ir-corticosterone, ir-ACTH, and pituitary ir-ACTH, also preventing the decrease in hypothalamic ir-CRH and ir-ACTH; while the mismatch oligonucleotide is nearly inactive. D) Role of endogenous opioid peptides in cardiovascular diseases. In collaboration with colleagues of the department of Internal Medicine we are evaluating plasma levels of endogenous opioids in patients affected by cardiovascular diseases with the aim to relate their levels with peculiar aspects of the pathological condition and to other plasma biochemical markers. Endogenous peptide levels (beta-endorphin, met-enkephalin, and nociceptin) are evaluated by radioimmunoassay adopting assays developed in our laboratory.