Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.
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.
Schiffer
W K
WK
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Gerasimov
M
M
Hofmann
L
L
Marsteller
D
D
Ashby
C R
CR
Brodie
J D
JD
Alexoff
D L
DL
Dewey
S L
SL
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*
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D020888:Vigabatrin; D010622:Phencyclidine; D004298:Dopamine