Feedback control of mesolimbic somatodendritic dopamine release in rat brain

Shafiqur Rahman, William J. McBride

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR-12909 (10-1,000 μM) or nomifensine (10-1,000 μM) dose-dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA. Coperfusion of 100 μM nomifensine with either 100 μM SCH-23390 (SCH), a D1 antagonist, or 100 μM sulpiride (SUL), a D2 receptor antagonist, produced either an additive (for SCH) or a synergistic (for SUL) elevation in the extracellular levels of DA in the ACB, whereas the reduction in the extracellular levels of DA in the VTA produced by nomifensine alone was completely prevented by addition of either antagonist. Application of 100 μM SCH or SUL alone through the microdialysis probe in the ACB increased the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA remained unchanged. Overall, the results suggest that (a) increasing the synaptic levels of DA in the ACB activates a long-loop negative feedback pathway to the VTA involving both D1 and D2 postsynaptic receptors and (b) terminal DA release within the ACB is regulated directly by D2 autoreceptors and may be indirectly regulated by D1 receptors, possibly on interneurons and/or through postsynaptic inhibition of the negative feedback loop.

Original languageEnglish (US)
Pages (from-to)684-692
Number of pages9
JournalJournal of Neurochemistry
Volume74
Issue number2
DOIs
StatePublished - Jan 29 2000

Keywords

  • Dopamine receptors
  • In vivo microdialysis
  • Negative feedback regulation
  • Nucleus accumbens
  • Somatodendritic dopamine release
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Feedback control of mesolimbic somatodendritic dopamine release in rat brain'. Together they form a unique fingerprint.

  • Cite this