GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats

Satoshi Ikemoto, Robert R. Kohl, William J. McBride

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 μM) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACB. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol, whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA levels in the ACB. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACB. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalJournal of Neurochemistry
Volume69
Issue number1
StatePublished - Jul 1997

Fingerprint

Ventral Tegmental Area
Nucleus Accumbens
GABA-A Receptors
Rats
Dopamine
Picrotoxin
GABA-A Receptor Antagonists
Muscimol
GABA-A Receptor Agonists
Injections
Bicuculline
Dopaminergic Neurons
Microdialysis
Microinjections
Metabolites
gamma-Aminobutyric Acid
Neurons
Chemical activation

Keywords

  • Dopamine
  • GABA(A) receptors
  • Microdialysis
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats. / Ikemoto, Satoshi; Kohl, Robert R.; McBride, William J.

In: Journal of Neurochemistry, Vol. 69, No. 1, 07.1997, p. 137-143.

Research output: Contribution to journalArticle

@article{e2b64c809c9942b3adc8fcffd6d23436,
title = "GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats",
abstract = "Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 μM) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACB. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol, whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA levels in the ACB. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACB. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.",
keywords = "Dopamine, GABA(A) receptors, Microdialysis, Nucleus accumbens, Ventral tegmental area",
author = "Satoshi Ikemoto and Kohl, {Robert R.} and McBride, {William J.}",
year = "1997",
month = "7",
language = "English",
volume = "69",
pages = "137--143",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats

AU - Ikemoto, Satoshi

AU - Kohl, Robert R.

AU - McBride, William J.

PY - 1997/7

Y1 - 1997/7

N2 - Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 μM) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACB. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol, whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA levels in the ACB. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACB. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.

AB - Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 μM) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACB. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol, whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA levels in the ACB. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACB. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.

KW - Dopamine

KW - GABA(A) receptors

KW - Microdialysis

KW - Nucleus accumbens

KW - Ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=0030949723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030949723&partnerID=8YFLogxK

M3 - Article

C2 - 9202304

AN - SCOPUS:0030949723

VL - 69

SP - 137

EP - 143

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -