We previously reported that brain-specific diacylglycerol kinase (DGK) delta-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKS deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGK delta interacted and co-localized with SERT. Furthermore, DGK delta-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression. Indeed, the amount of 5-HT in the cerebral cortex was significantly decreased in DGK delta-KO mice. These data strongly suggest that OCD-like behaviors in the DGK delta-KO mice are caused by comprehensive and composite serotonergic hypofunction. (C) 2018 Elsevier Inc. All rights reserved.