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Reduction in phencyclidine induced sensorimotor gating deficits in the rat following increased system x(c) (-) activity in the medial prefrontal cortex.
MedLine Citation:
PMID:  23192314     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System x(c) (-), a cystine-glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. OBJECTIVES: Our goal was to determine whether increased system x(c) (-) activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. METHODS: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system x(c) (-), in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3-3 mg/kg, sc). N-Acetylcysteine (10-100 μM) and the system x(c) (-) inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system x(c) (-) activity, respectively. The uptake of (14)C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system x(c) (-) activity. RESULTS: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of (14)C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10-100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system x(c) (-). CONCLUSIONS: These results indicate that phencyclidine disrupts sensorimotor gating through system x(c) (-) independent mechanisms, but that increasing cystine-glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine.
Authors:
Victoria Lutgen; Krista Qualmann; Jon Resch; Linghai Kong; Sujean Choi; David A Baker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-29
Journal Detail:
Title:  Psychopharmacology     Volume:  -     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biomedical Sciences, Marquette University, Suite 446, 561 N. 15th St, Milwaukee, WI, 53233, USA.
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