We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation.
- Authors
Kumar, Gaurav; Olley, Joseph; Steckler, Thomas; Talpos, John
- Abstract
Rationale: N-methyl- d-aspartate (NMDA) receptors play crucial roles in learning and memory, but the role of each NMDA receptor subtype in a specific cognitive process is unclear. Non-selective blockers of NMDA receptor are used to model the cognitive impairment in schizophrenia and Alzheimer's disease. Counter-intuitively selective NR2A and 2B NMDA receptor antagonists are thought to have pro-cognitive properties. These seemingly contrasting findings might in part be the result of different compounds and behavioral measures used across studies. Objective: We compared the effect of NVP-AAM077 (NR2A antagonist), CP 101-606 (NR2B antagonist), and MK-801 (non-selective antagonist) in a series of touch screen tasks that can be used to measure spatial cognition and cognitive flexibility. Methods: NVP-AAM077, CP 101-606, and MK-801 were administered prior to testing, in adult male Lister-hooded rats trained in tasks of location discrimination, paired associate learning (PAL), and trial unique non-match to location (TUNL). Results: Results showed that MK-801 impaired performance on all the tasks. In contrast, CP 101-606 only impaired reversal learning in location discrimination and had minimal effect on working memory in TUNL and caused a modest improvement in accuracy in PAL and acquisition of a spatial discrimination. NVP-AAM077 had little effect on performance across tasks, although these data allude to a potential enhancement of acquisition of a spatial location and impairments in spatial reversal learning in a separation-dependent manner. Conclusions: These data demonstrated that non-selective NMDA antagonism will disrupt numerous aspects of cognitive function. However, selective antagonism is capable of impairing or enhancing cognitive function in a task-dependent fashion.
- Subjects
METHYL aspartate receptors; MILD cognitive impairment; MEMORY disorders; LEARNING; ALZHEIMER'S patients; PEOPLE with schizophrenia
- Publication
Psychopharmacology, 2015, Vol 232, Issue 21/22, p3991
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-015-4008-9