Document Detail

A rat model for neural circuitry abnormalities in schizophrenia.
MedLine Citation:
PMID:  17406315     Owner:  NLM     Status:  MEDLINE    
Animal models for complex brain disorders, such as schizophrenia, are essential for the interpretation of postmortem findings. These models allow empirical testing of hypotheses regarding the role of genetic and environmental factors, the pathophysiological mechanisms and brain circuits that are responsible for specific neural abnormalities and their associated behavioral impairment, and the effectiveness of therapeutic treatments relative to these diseases. Recently, we developed a rodent model for neural circuitry abnormalities in discrete corticolimbic subregions of subjects with major psychoses. According to our protocol, the GABA-A receptor antagonist picrotoxin is stereotaxically infused in the basolateral amygdala to mimic a GABA defect in this region that is postulated to occur in these disorders. This protocol has been tested with a number of acute and chronic time schedules. Following picrotoxin administration in the basolateral amygdala, changes in GABAergic neurons and/or terminals in hippocampal regions CA2/3 are observed, similar to those seen in major psychoses, as well as a marked reduction in GABA-receptor-mediated currents in pyramidal neurons of this region. This has established the construct and predictive validity of this model for studying limbic-lobe circuitry abnormalities. We propose that this modeling strategy may provide a valid alternative to isomorphic models of these diseases.
Sabina Berretta; Francine M Benes
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature protocols     Volume:  1     ISSN:  1750-2799     ISO Abbreviation:  Nat Protoc     Publication Date:  2006  
Date Detail:
Created Date:  2007-04-04     Completed Date:  2007-09-21     Revised Date:  2008-03-24    
Medline Journal Info:
Nlm Unique ID:  101284307     Medline TA:  Nat Protoc     Country:  England    
Other Details:
Languages:  eng     Pagination:  833-9     Citation Subset:  IM    
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Disease Models, Animal*
GABA Antagonists / pharmacology*
Hippocampus / cytology
Neurons / drug effects,  metabolism,  pathology
Picrotoxin / pharmacology*
Rats, Sprague-Dawley
Schizophrenia / chemically induced*,  pathology,  physiopathology*
Reg. No./Substance:
0/GABA Antagonists; 124-87-8/Picrotoxin

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

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