Negative interaction of dopamine D2 receptor antagonists and GBR 12909 and GBR 12935 dopamine uptake inhibitors in the nucleus accumbens

Shafiqur Rahman, Eric Engleman, Jay Simon, William J. McBride

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The objective of this study was to examine the interaction of dopamine D2 receptor antagonists and dopamine uptake inhibitors on the regulation of extracellular dopamine release in the nucleus accumbens of Wistar rats employing in vivo microdialysis and in vitro dopamine uptake studies. Application of the D2 receptor antagonists raclopride (100 μm) or sulpiride (100 μm) alone through the microdialysis probe in the nucleus accumbens for 60 min increased the extracellular levels of dopamine in the nucleus accumbens to 150% and 200% of basal, respectively. Perfusion of the nucleus accumbens for 60 min with the dopamine uptake inhibitors, 1-[2-[bis(4-Fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909; 100 μm) or 1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine dihydrochloride (GBR 12935; 100 μm) alone, increased the extracellular levels of dopamine in the nucleus accumbens to 400% and 350% of basal, respectively. Co-perfusion of 100 μM GBR 12909 or GBR 12935 with either 100 μM sulpiride or raclopride produced a significant reduction in the GBR 12909 or GBR 12935 induced increase in the extracellular levels of dopamine to basal levels. In vitro, GBR 12909 (1-9 nM) dose-dependently inhibited active uptake of [3H]dopamine in homogenates of the nucleus accumbens. Addition of 100 μm sulpiride had little effect on GBR 12909 inhibition of [3H] dopamine uptake, suggesting that dopamine D2 receptor antagonists are not blocking the actions of the GBR-type dopamine uptake inhibitors at the dopamine transporter. Overall, the data suggest that complex interactions occur in vivo between D2 antagonists and GBR-type dopamine uptake inhibitors, which negate their effects on elevating the extracellular levels of dopamine in the nucleus accumbens.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalEuropean Journal of Pharmacology
Volume414
Issue number1
DOIs
StatePublished - Feb 23 2001

Keywords

  • Dopamine uptake
  • GBR 12909
  • GBR 12935
  • In vivo
  • Microdialysis
  • Nucleus accumbens
  • Raclopride
  • Sulpiride

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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