Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats

Zheng Ming Ding, Wen Liu, Eric Engleman, Zachary Rodd, William J. McBride

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABAA antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 μM) into the posterior VTA increased extracellular dopamine levels locally (80% above baseline) and in the ACB shell and core (70% above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30% above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 μM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABAA receptor-mediated tonic inhibition.

Original languageEnglish
Pages (from-to)404-412
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume92
Issue number3
DOIs
StatePublished - May 2009

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GABA-A Receptor Antagonists
Ventral Tegmental Area
Dopaminergic Neurons
Neurons
Wistar Rats
Rats
Dopamine
Picrotoxin
Sulpiride
Microdialysis
GABA-A Receptors
Dopamine D2 Receptor Antagonists
Reinforcement
Tegmentum Mesencephali
Nucleus Accumbens
Microinjections
Pharmaceutical Preparations

Keywords

  • Dopamine
  • Dopamine receptor
  • GABA receptor
  • Microdialysis
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

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title = "Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats",
abstract = "Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABAA antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 μM) into the posterior VTA increased extracellular dopamine levels locally (80{\%} above baseline) and in the ACB shell and core (70{\%} above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30{\%} above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 μM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABAA receptor-mediated tonic inhibition.",
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T1 - Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats

AU - Ding, Zheng Ming

AU - Liu, Wen

AU - Engleman, Eric

AU - Rodd, Zachary

AU - McBride, William J.

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N2 - Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABAA antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 μM) into the posterior VTA increased extracellular dopamine levels locally (80% above baseline) and in the ACB shell and core (70% above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30% above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 μM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABAA receptor-mediated tonic inhibition.

AB - Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABAA antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 μM) into the posterior VTA increased extracellular dopamine levels locally (80% above baseline) and in the ACB shell and core (70% above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30% above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 μM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABAA receptor-mediated tonic inhibition.

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