2,5-dimethoxy-4-iodoamphetamine (also known as DOI) is a hallucinogenic Serotonin_2A Receptor agonist. In this presentation, we demonstrate the effects of a psychedelic substance DOI on behaviors associated with spatial memory, mood, and motor coordination. Administration of DOI (1.0 mg/kg, s,c,) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice, with no alterations in horizontal spontaneous locomotion. The decrease in the Y-maze alternations was completely recovered by administration with volinanserin (0.1 mg/kg, i.p.), a selective and potent 5-HT₂ receptor antagonist. No effect of DOI on motor coordination and ambulatory activity was observed based on the observations in the rotarod and pole tests. A reduction in buried marbles was observed in DOI-treated mice measured in the marble-burying test.  Reduced exploratory time was observed in mice after administration of DOI in a novel-object exploration test. These observations suggest that DOI induces impairments in spatial short-term memory and retrieval and mood but not locomotor hyperactivity or dysfunction of motor coordination. Supported by Ministry of Health, Labor and Welfare Grants-in-Aid for Scientific Research (22KC1005).