Document Detail


N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.
MedLine Citation:
PMID:  23311352     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning.
Authors:
R G M Morris; R J Steele; J E Bell; S J Martin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  The European journal of neuroscience     Volume:  37     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-08-16     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  700-17     Citation Subset:  IM    
Copyright Information:
© 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
2-Amino-5-phosphonovalerate / administration & dosage,  pharmacology*
Animals
Cerebral Cortex / cytology,  drug effects,  physiology
Cues
Excitatory Amino Acid Antagonists / administration & dosage,  pharmacology*
Female
Hippocampus / cytology,  drug effects,  physiology
Infusions, Intraventricular
Infusions, Spinal
Male
Maze Learning / drug effects*
Memory / drug effects*
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
G0700447//Medical Research Council; G9200370//Medical Research Council
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate; 76726-92-6/2-Amino-5-phosphonovalerate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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