Document Detail


Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.
MedLine Citation:
PMID:  11682254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To explore the role of endogenous GABA in NMDA antagonist induced dopamine (DA) release, we used in vivo microdialysis to study the effects of pretreatment with gamma-vinyl GABA (GVG) on phencyclidine (PCP)-induced DA release in terminal regions of midbrain DA neurons. GVG, an irreversible inhibitor of the GABA catabolizing enzyme GABA-AT, significantly reduced the DA response to PCP (7.0 mg/kg) in freely moving animals. Preferential increases in PCP-induced DA release in the PFC (four-fold those of NAcc) were dose-dependently inhibited by acute pretreatment with GVG at doses of 150 (51% inhibition), 300 (68% inhibition), and 500 (82% inhibition) mg/kg, whereas NAcc PCP-induced DA activity was unresponsive to 150 mg/kg and only partially inhibited by 300 and 500 mg/kg. Subchronic treatment with GVG did not enhance the inhibitory capacity of the GABAergic system. While GVG evidently modulates PCP-induced increases in mesocorticolimbic DA transmission, the character of this modulation is regionally specific, with cortical NMDA-antagonist induced increases appearing more sensitive to inhibition by endogenous GABA than subcortical areas.
Authors:
W K Schiffer; M Gerasimov; L Hofmann; D Marsteller; C R Ashby; J D Brodie; D L Alexoff; S L Dewey
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  25     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-29     Completed Date:  2002-01-03     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  704-12     Citation Subset:  IM    
Affiliation:
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticonvulsants / pharmacology*
Cerebral Cortex / drug effects*
Dopamine / physiology*
Excitatory Amino Acid Antagonists / pharmacology*
Extracellular Space / drug effects,  metabolism
Limbic System / drug effects*
Male
Nucleus Accumbens / metabolism
Phencyclidine / pharmacology
Prefrontal Cortex / metabolism
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Stereotaxic Techniques
Synaptic Transmission / drug effects*
Vigabatrin / pharmacology*
Grant Support
ID/Acronym/Agency:
5RO-DA06278/DA/NIDA NIH HHS; MH 49165/MH/NIMH NIH HHS; R29 MH 55155/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate; 60643-86-9/Vigabatrin; 77-10-1/Phencyclidine

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


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