Fig. 1: Experimental timeline.

Male and female BALB/c mice were treated for 4 consecutive weeks during adolescence (postnatal day [PD] 35–62) or adulthood (PD 60–87) either thrice-weekly (M–W–F) or daily with either (R,S)-ketamine (KET) or its metabolite, (2R,6R)-hydroxynorketamine (HNK). For thrice-weekly drug administration, mice received a saline injection on Tuesday, Thursday, Saturday, and Sunday to control for the handling and stress of the injection. Memory performance was assessed beginning 10 days after drug cessation in three operationally distinct tasks: (1) novel object recognition to assess explicit memory, (2) Y-maze to assess working memory, and (3) passive avoidance to assess implicit memory.