Autism Spectrum Disorders (ASDs) are complex neurodevelopmental conditions characterized by deficits in social interaction, communication and cognitive flexibility. In the search of possible etiopathological mechanisms of ASDs, multiple studies linked aberrant mesolimbic reward pathway to dysfunction in sociability and restricted behaviors. However, the lateral habenula (LHb), representing the anti-reward center of the central nervous system, has been neglected so far. LHb activity encodes aversive responses and inhibits the physiological dynamics of ventral tegmental area (VTA), interfering with reward perception. Furthermore, magnetic resonance imaging revealed that the habenula is significantly enlarged in children and adults with ASDs. We hypothesized that aberrant activity in the LHb-VTA pathway might engender a dysfunctional control of motivated behaviors, that translates into the ASDs endophenotypes. We found that the chemogenetic activation of LHb in wild-type (WT) animals causes a strong decrease of sociability in the three-chamber test, with no effects on the global locomotor activity of mice. Moreover, the same manipulation produces a significant reduction of cognitive flexibility in a classical paradigm of operant conditioning. In contrast, we did not detect any difference in self-grooming behavior following LHb activation. These results suggest that an exaggerated activation of LHb neurons results in the failure of reward mechanisms, generating in WT animals social and cognitive alterations comparable to core ASDs traits.