Document Detail


Abnormal neurotransmitter release underlying behavioral and cognitive disorders: toward concepts of dynamic and function-specific dysregulation.
MedLine Citation:
PMID:  17164812     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abnormalities in the regulation of neurotransmitter release and/or abnormal levels of extracellular neurotransmitter concentrations have remained core components of hypotheses on the neuronal foundations of behavioral and cognitive disorders and the symptoms of neuropsychiatric and neurodegenerative disorders. Furthermore, therapeutic drugs for the treatment of these disorders have been developed and categorized largely on the basis of their effects on neurotransmitter release and resulting receptor stimulation. This perspective stresses the theoretical and practical implications of hypotheses that address the dynamic nature of neurotransmitter dysregulation, including the multiple feedback mechanisms regulating synaptic processes, phasic and tonic components of neurotransmission, compartmentalized release, differentiation between dysregulation of basal vs activated release, and abnormal release from neuronal systems recruited by behavioral and cognitive activity. Several examples illustrate that the nature of the neurotransmitter dysregulation in animal models, including the direction of drug effects on neurotransmitter release, depends fundamentally on the state of activity of the neurotransmitter system of interest and on the behavioral and cognitive functions recruiting these systems. Evidence from evolving techniques for the measurement of neurotransmitter release at high spatial and temporal resolution is likely to advance hypotheses describing the pivotal role of neurotransmitter dysfunction in the development of essential symptoms of major neuropsychiatric disorders, and also to refine neuropharmacological mechanisms to serve as targets for new treatment approaches. The significance and usefulness of hypotheses concerning the abnormal regulation of the release of extracellular concentrations of primary messengers depend on the effective integration of emerging concepts describing the dynamic, compartmentalized, and activity-dependent characteristics of dysregulated neurotransmitter systems.
Authors:
Martin Sarter; John P Bruno; Vinay Parikh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2006-12-13
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  32     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-14     Completed Date:  2007-08-31     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1452-61     Citation Subset:  IM    
Affiliation:
Department of Psychology, University of Michigan, Ann Arbor, MI 48109-1043, USA. msarter@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism*,  physiopathology
Brain Chemistry / physiology
Cognition Disorders / metabolism*,  physiopathology
Humans
Mental Disorders / metabolism*,  physiopathology
Neurotransmitter Agents / metabolism*,  secretion
Synaptic Transmission / physiology*
Grant Support
ID/Acronym/Agency:
DA019502/DA/NIDA NIH HHS; KO2MH10172/MH/NIMH NIH HHS; MH057436/MH/NIMH NIH HHS; MH063114/MH/NIMH NIH HHS; MH073600/MH/NIMH NIH HHS; NS37026/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neurotransmitter Agents

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


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