Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission

Citation
Wk. Schiffer et al., Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission, NEUROPSYCH, 25(5), 2001, pp. 704-712
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROPSYCHOPHARMACOLOGY
ISSN journal
0893-133X → ACNP
Volume
25
Issue
5
Year of publication
2001
Pages
704 - 712
Database
ISI
SICI code
0893-133X(200111)25:5<704:GVDMNA>2.0.ZU;2-V
Abstract
To explore the role of endogenous GABA in NMDA antagonist induced dopamine (DA) release, we used in vivo microdialysis to study the effects of pretrea tment with gamma -vinyl GABA (GVG) on phencyclidine (PCP)-induced DA releas e in terminal regions of midbrain DA neurons. GVG, an irreversible inhibito r of the GABA catabolizing enzyme GABA-AT, significantly reduced the DA res ponse to PCP (TO mg/kg) in freely moving animals. Preferential increases in PCP-induced DA release in the PFC (four-fold those of NAcc) were dose-depe ndently inhibited by acute pretreatment with GVG at doses of 150 (51% inhib ition), 300 (68% inhibition), and 500 (82% inhibition) mg/kg, whereas NAcc PCP-induced DA activity was unresponsive to 150 mg/kg and only partially in hibited by 300 and 500 mg/kg. Subchronic treatment with GVG did not enhance the inhibitory capacity of the GABAergic system. While GVG evidently modul ates PCP-induced increases in mesocorticolimbic DA transmission, the charac ter of this modulation is regionally specific, with cortical NMDA-antagonis t induced increases appearing more sensitive to inhibition by endogenous GA BA than subcortical areas. (C) 2001 American College of Neuropsychopharmaco logy. Published by Elsevier Science Inc.