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Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation.

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.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Kumar G,Olley J,Steckler T,Talpos J

doi

10.1007/s00213-015-4008-9

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

3991-4003

issue

21-22

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-015-4008-9

journal_volume

232

pub_type

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