Selective cognitive impairments associated with NMDA receptor blockade in humans.
Publication/Presentation Date
3-1-2005
Abstract
Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) may be involved in the pathophysiology of schizophrenia. NMDAR antagonists like ketamine induce schizophrenia-like features in humans. In rodent studies, NMDAR antagonism impairs learning by disrupting long-term potentiation (LTP) in the hippocampus. This study investigated the effects of ketamine on spatial learning (acquisition) vs retrieval in a virtual Morris water task in humans. Verbal fluency, working memory, and learning and memory of verbal information were also assessed. Healthy human subjects participated in this double-blinded, placebo-controlled study. On two separate occasions, ketamine/placebo was administered and cognitive tasks were assessed in association with behavioral ratings. Ketamine impaired learning of spatial and verbal information but retrieval of information learned prior to drug administration was preserved. Schizophrenia-like symptoms were significantly related to spatial and verbal learning performance. Ketamine did not significantly impair attention, verbal fluency, or verbal working memory task performance. Spatial working memory was slightly impaired. In conclusion, these results provide evidence for ketamine's differential impairment of verbal and spatial learning vs retrieval. By using the Morris water task, which is hippocampal-dependent, this study helps bridge the gap between nonhuman animal and human NMDAR antagonism research. Impaired cognition is a core feature of schizophrenia. A better understanding of NMDA antagonism, its physiological and cognitive consequences, may provide improved models of psychosis and cognitive therapeutics.
Volume
30
Issue
3
First Page
633
Last Page
639
ISSN
0893-133X
Published In/Presented At
Rowland, L. M., Astur, R. S., Jung, R. E., Bustillo, J. R., Lauriello, J., & Yeo, R. A. (2005). Selective cognitive impairments associated with NMDA receptor blockade in humans. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 30(3), 633–639. https://doi.org/10.1038/sj.npp.1300642
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
15647751
Department(s)
Administration and Leadership
Document Type
Article