title: Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.
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 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.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Schiffer
authors.forename: M
authors.initials: M
authors.lastname: Gerasimov
authors.forename: L
authors.initials: L
authors.lastname: Hofmann
authors.forename: D
authors.initials: D
authors.lastname: Marsteller
authors.forename: C R
authors.initials: CR
authors.lastname: Ashby
authors.forename: J D
authors.initials: JD
authors.lastname: Brodie
authors.forename: D L
authors.initials: DL
authors.lastname: Alexoff
authors.forename: S L
authors.initials: SL
authors.lastname: Dewey
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013238:Stereotaxic Techniques; D009435:Synaptic Transmission / Q000187:drug effects*; D020888:Vigabatrin / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D020888:Vigabatrin; D010622:Phencyclidine; D004298:Dopamine