Involvement of GABA and cholinergic receptors in the nucleus accumbens on feedback control of somatodendritic dopamine release in the ventral tegmental area

Shafiqur Rahman, William J. McBride

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The objectives of the present study were to examine the involvement of GABA and cholinergic receptors within the nucleus accumbens (ACB) on feedback regulation of somatodendritic dopamine (DA) release in the ventral tegmental area (VTA). Adult male Wistar rats were implanted with ipsilateral dual guide cannulae for in vivo microdialysis studies. Activation of the feedback system was accomplished by perfusion of the ACB with the DA uptake inhibitor GBR 12909 (GBR; 100 μM). To assess the involvement of GABA and cholinergic receptors in regulating this feedback system, antagonists (100 μM) for GABAA (bicuculline, BIC), GABAB (phaclofen, PHAC), muscarinic (scopolamine, SCOP), and nicotinic (mecamylamine, MEC) receptors were perfused through the probe in the ACB while measuring extracellular DA levels in the ACB and VTA. Local perfusion of the ACB with GBR significantly increased (500% of baseline) the extracellular levels of DA in the ACB and produced a concomitant decrease (50% of baseline) in the extracellular DA levels in the VTA. Perfusion of the ACB with BIC or PHAC alone produced a 200-400% increase in the extracellular levels of DA in the ACB but neither antagonist altered the levels of DA in the VTA. Co-perfusion of either GABA receptor antagonist with GBR further increased the extracellular levels of DA in the ACB to 700-800% of baseline. However, coperfusion with BIC completely prevented the reduction in the extracellular levels of DA in the VTA produced by GBR alone, whereas PHAC partially prevented the reduction. Local perfusion of the ACB with either MEC or SCOP alone had little effect on the extracellular levels of DA in the ACB or VTA. Co-perfusion of either cholinergic receptor antagonist with GBR markedly reduced the extracellular levels of DA in the ACB and prevented the effects of GBR on reducing DA levels in the VTA. Overall, the results of this study suggest that terminal DA release in the ACB is under tonic GABA inhibition mediated by GABAA (and possibly GABAB) receptors, and tonic cholinergic excitation mediated by both muscarinic and nicotinic receptors. Activation of GABAA (and possibly GABAB) receptors within the ACB may be involved in the feedback inhibition of VTA DA neurons. Cholinergic interneurons may influence the negative feedback system by regulating terminal DA release within the ACB.

Original languageEnglish
Pages (from-to)646-654
Number of pages9
JournalJournal of Neurochemistry
Volume80
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Ventral Tegmental Area
GABA Receptors
Nucleus Accumbens
Cholinergic Receptors
Feedback control
Dopamine
Perfusion
Bicuculline
Feedback
Mecamylamine
Cholinergic Agents
Scopolamine Hydrobromide
Nicotinic Receptors
Dopamine Uptake Inhibitors
Chemical activation
GABA Antagonists
Dopaminergic Neurons
Microdialysis
Cholinergic Antagonists
Muscarinic Receptors

Keywords

  • Cholinergic receptors
  • Dopamine
  • Feedback regulation
  • GABA receptors
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Involvement of GABA and cholinergic receptors in the nucleus accumbens on feedback control of somatodendritic dopamine release in the ventral tegmental area. / Rahman, Shafiqur; McBride, William J.

In: Journal of Neurochemistry, Vol. 80, No. 4, 2002, p. 646-654.

Research output: Contribution to journalArticle

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