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

Wynne K. Schiffer, Madina Gerasimov, Lauren Hofmann, Douglas Marsteller, Charles R. Ashby, Jonathan D. Brodie, David L. Alexoff, Stephen L. Dewey

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 γ-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.

Original languageEnglish (US)
Pages (from-to)704-712
Number of pages9
JournalNeuropsychopharmacology
Volume25
Issue number5
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This research was carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886), the National Institutes of Mental Health (NIMH MH49165 and NIMH R2955155), and the National Institute on Drug Abuse (5RO-DA06278). Partial funding provided by Eli Lilly Pharmaceuticals, Inc.

Keywords

  • Dopamine
  • GABA
  • Glutamate
  • Microdialysis
  • NMDA-antagonist
  • Phencyclidine
  • Vigabatrin

Fingerprint

Dive into the research topics of 'Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission'. Together they form a unique fingerprint.

Cite this