The neuropeptide oxytocin (OXT) regulates a number of socio-emotional behaviors in mice, including parental care, pair-bonding, social memory, and social aggression by activating OXT receptors (OXTR). Both distribution and number of OXT receptors in the brain affect the type and degree of behavioural responses. Many factors, such as early life stress (Lukas et al., 2010) and poor social rearing conditions (Ahern and Young, 2009), have been shown to cause a reduction in brain OXTRs linked to an impairment in social functioning. Moreover, prolonged pharmacological treatments with neurotrasmitters or neuropeptides can produce variations of receptor expression (receptors desensitization or up-regulation) in the brain. When C57BL/6J male mice were daily treated with intranasal OXT (0.15 IU and 0.3 IU) for 15 days (Huang et al., 2013) we observed a greater reduction of OXTRs (-20%) in limbic brain areas involved in social behavior (i.e. amygdala) compared to a lesser reduction of OXTRs (-10%) in areas involved in memory and social cognition (i.e. hippocampus, lateral septum). This receptor down-regulation was accompanied by an impairment in social behaviors towards same and opposite sex and towards familiar and unfamiliar subjects.We have also observed that genetically manipulated mice, with a total absence of OXTRs (Oxtr-/-; Sala et al. 2011) in the brain exhibit specific social deficits, increased aggression and impaired cognitive flexibility. However, heterozygous (Oxtr+/-) mice, with approximately 50% fewer oxytocin receptors (OXTRs) in the brain than the wild type, show impaired social behaviours but not increased aggression or cognitive inflexibility.Our study indicates that the reduction of the OXTRs affects specific behaviours in a dose-dependent manner: social behaviour is sensitive to even a partial reduction in OXTR expression, whereas increased aggression and impairment in cognitive flexibility occures when the OXTRs are completely absent.