Background Oxytocin (OXT) is a mammalian hormone involved in lactation and parturition that also acts as a neurotransmitter in the brain. In humans, oxytocin is involved in social recognition and bonding, trust between people and generosity. A recent study found that oxytocin could treat some of the symptoms of Prader-Willi-Syndrome (PWS) and a pilot clinical study in ongoing in France to treat newborn PWS babies with oxytocin. Aim of this project was to contribute to develop an oxytocin-based treatment for PWS patients  by 1) achieving a better understanding of the role of brain OXT 2) developing OXT-like molecules active on specific brain cellular targets. Results Concerning the first aim, we discovered that OXT plays an important role in neuronal excitability in the first days of post-natal life by regulating the expression of a protein involved in the homeostasis of chlorine. This, in turn, may affect the development of neuronal circuits in the brain. Concerning the second aim, we focused on Carbetocin, a molecule similar to OXT that has been proposed as a treatment for PWS. However, our studies  indicate that Carbetocin does not mirror OXT effects and thus is should be further characterized before clinical use in patients. Finally, we synthesized and characterized a series of new OXT-like molecules that displayed an increased efficacy as compared to OXT in preclinical models. Perspective We believe that the identification of the brain targets of OXT and the characterization of new OXT-like analogs will contribute and foster the development of an OXT-based treatment  in PWS.