Document Detail

Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task.
MedLine Citation:
PMID:  11271408     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Understanding the mechanistic basis of working memory, the capacity to hold representation "on line," is important for delineating the processes involved in higher cognitive functions and the pathophysiology of thought disorders. OBJECTIVES: We compared the contribution of glutamate and dopamine receptor subtypes to temporal aspects of working memory using a modified rodent spatial working memory task that incorporates important elements of clinical working memory tasks. METHODS: A discrete paired-trial variable-delay T-maze task was used. Initial characterization studies indicated that performance on this task is stable at seconds-long retention intervals, is sensitive to retention interval and proactive interference, and is dependent on the integrity of the medial prefrontal cortex. RESULTS: Consistent with clinical findings, low dose amphetamine (0.25 mg/kg) produced a delay-dependent improvement in performance, while higher doses impaired performance at all retention intervals. D1 receptor blockade produced the predicted dose- and delay-dependent impairment. D2 receptor blockade had no effect. Activation of metabotropic glutamate 2/3 (mGluR2/3) receptors, which in the prefrontal cortex inhibits the slow asynchronous phase of glutamate release, also produced a delay-dependent impairment. Low doses of an AMPA/kainate antagonist had effects similar to the mGluR2/3 agonist. In contrast, NMDA receptor antagonist-induced impairment was memory load-insensitive, resulting in chance-level performance at all retention intervals. CONCLUSIONS: These findings suggest that activation of NMDA receptors is necessary for the formation of mnemonic encoding while modulatory components involving slow asynchronous release of glutamate and phasic release of dopamine contribute to the active maintenance of information during the delay period.
J M Aultman; B Moghaddam
Related Documents :
25061928 - An electrophysiological dissociation between orbitofrontal reality filtering and contex...
24625268 - Negative differential resistance behavior and memory effect in laterally bridged zno na...
23313868 - Glucocorticoids in the dorsomedial striatum modulate the consolidation of spatial but n...
21892988 - Impaired visual scanning and memory for faces in high-functioning autism spectrum disor...
22685098 - Anthropology's disenchantment with the cognitive revolution(1).
12201338 - Does node stability underlie the verbal transformation effect? a test of node structure...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychopharmacology     Volume:  153     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-05-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  353-64     Citation Subset:  IM    
Department of Psychiatry, Yale University School of Medicine, VA Medical Center, West Haven, CT 06516, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Amphetamine / pharmacology
Dopamine Antagonists / pharmacology*
Excitatory Amino Acid Antagonists / pharmacology*
Muscarinic Antagonists / pharmacology*
Prefrontal Cortex / injuries
Rats, Sprague-Dawley
Receptors, Dopamine / drug effects*,  physiology
Receptors, Glutamate / drug effects*,  physiology
Receptors, N-Methyl-D-Aspartate / drug effects,  physiology
Retention (Psychology) / drug effects*,  physiology
Scopolamine / pharmacology
Grant Support
Reg. No./Substance:
0/Dopamine Antagonists; 0/Excitatory Amino Acid Antagonists; 0/Muscarinic Antagonists; 0/Receptors, Dopamine; 0/Receptors, Glutamate; 0/Receptors, N-Methyl-D-Aspartate; 300-62-9/Amphetamine; 51-34-3/Scopolamine

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

Previous Document:  Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral a...
Next Document:  8-OH-DPAT, but not deramciclane, antagonizes the anxiogenic-like action of paroxetine in an elevated...