Impaired Spatial Memory after Ketamine Administration in Chronic Low Doses

Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a dissociative anesthetic, presently included in the category of the psychoactive substances known as “club drugs”. Ketamine administration was associated with impaired working memory and increased psychopathological symptoms, but there is a lack of information regarding the effects of chronic sub-anesthetic doses. Adult Wistar rats were administered ketamine, 5 and 10 mg/kg twice daily, subcutaneously for 14 days. One week later, rats were tested in an object recognition/object location task and in the open field arena. There was altered performance in both the object recognition/location and in the open field tests by the group chronically exposed to the lower dose of ketamine. These animals displayed a decreased discrimination index (p<0.05) in the object recognition task, were unable to recognize the displacement of a familiar object and displayed decreased activity across open filed sessions. Importantly, these alterations were not observed in animals administered a higher dose of ketamine. Collectively, these results consistently show that chronic administration of ketamine in sub-anesthetic doses may lead to decreased habituation and inability to update spatial representations.