Linked Life Data

15010696

Source:http://linkedlifedata.com/resource/pubmed/id/15010696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Pharmacological manipulation of N-methyl-D-aspartate (NMDA) receptors may be critical for the treatment of many neurological and psychiatric disorders. Metabotropic glutamate (mGlu5) receptors are abundant in corticolimbic circuitry, where they modulate NMDA receptor-mediated signal transduction. Therefore, pharmacological manipulation of mGlu5 receptor may provide a treatment strategy for cognitive disorders that are associated with NMDA receptor dysfunction. We sought to determine whether the recently described molecular and cellular interactions between NMDA and mGlu5 receptors coregulate higher order behaviors. We examined the interaction of the selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and the use-dependent NMDA antagonist MK-801, on locomotion, stereotypy, working memory, instrumental learning, and corticolimbic dopamine release. MPEP, at 10 mg/kg, but not 3 mg/kg, impaired working memory and instrumental learning, transiently increased dopamine release in prefrontal cortex and nucleus accumbens, and augmented the effect of MK-801 on cortical dopamine release, locomotion, and stereotypy. Pretreatment with 3 mg/kg of MPEP enhanced the detrimental effects of MK-801 on cognition. These results demonstrate that an mGlu5 receptor antagonist can potentiate the motoric, cognitive, and dopaminergic effects of an NMDA receptor antagonist. Thus, mGlu5 receptors appear to play a major role in regulating NMDA receptor-dependent cognitive functions such as learning and working memory. By extension, these results suggest that pharmacological potentiation of mGlu5 receptors may ameliorate the cognitive and other behavioral abnormalities associated with NMDA receptor deficiency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0893-133X
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Nature Publishing Group
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1259-69
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:15010696-Analysis of Variance, pubmed-meshheading:15010696-Animals, pubmed-meshheading:15010696-Behavior, Animal, pubmed-meshheading:15010696-Conditioning, Operant, pubmed-meshheading:15010696-Dizocilpine Maleate, pubmed-meshheading:15010696-Dopamine, pubmed-meshheading:15010696-Dose-Response Relationship, Drug, pubmed-meshheading:15010696-Drug Interactions, pubmed-meshheading:15010696-Excitatory Amino Acid Antagonists, pubmed-meshheading:15010696-Male, pubmed-meshheading:15010696-Maze Learning, pubmed-meshheading:15010696-Memory, Short-Term, pubmed-meshheading:15010696-Microdialysis, pubmed-meshheading:15010696-Motor Activity, pubmed-meshheading:15010696-Pyridines, pubmed-meshheading:15010696-Rats, pubmed-meshheading:15010696-Rats, Sprague-Dawley, pubmed-meshheading:15010696-Receptors, Metabotropic Glutamate, pubmed-meshheading:15010696-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:15010696-Stereotyped Behavior
pubmed:year
2004
pubmed:articleTitle
Functional Interaction Between NMDA and mGlu5 Receptors: Effects on Working Memory, Instrumental Learning, Motor Behaviors, and Dopamine Release.
pubmed:affiliation
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.