title: Ketamine impairs multiple cognitive domains in rhesus monkeys.
abstract: Available evidence suggests that recreational use and abuse of the dissociative anaesthetic ketamine is increasing. Characterization of the cognitive risks of ketamine exposure contributes substantially to understanding this growing public health threat. Although prior human studies demonstrate that ketamine impairs a range of cognitive skills, investigation in nonhuman models permits more precise exploration of neurochemical mechanisms which may underlie detrimental behavioral effects. Adult male rhesus monkeys (N=7) were trained on a neuropsychological battery including tests of memory (delayed match-to-sample, DMS; self-ordered spatial search, SOSS), reaction time (RT), reinforcer efficacy and sustained attention (progressive ratio, PR) and fine motor coordination (bimanual motor skill, BMS). Battery performance was then serially challenged with acute doses of ketamine (0.3, 1.0, 1.78 mg/kg IM). Ketamine impaired DMS and SOSS in a dose x difficulty dependent manner with the most difficult task conditions disrupted at the 1.0 and 1.78 mg/kg doses. Thus, both visual recognition memory and working memory indices were affected. Ketamine also slowed RT and BMS performance and interfered with PR performance at the 1.78 mg/kg dose. Overall the present findings confirm that ketamine interferes with multiple aspects of cognition at subanesthetic doses in monkeys.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mtaffe@scripps.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Taffe
authors.forename: Sophia A
authors.initials: SA
authors.lastname: Davis
authors.forename: Tannia
authors.initials: T
authors.lastname: Gutierrez
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Gold
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D016202:N-Methylaspartate / Q000378:metabolism; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013647:Task Performance and Analysis
chemical_list: D000778:Anesthetics, Dissociative; D016202:N-Methylaspartate; D007649:Ketamine