D1-D2 interaction in feedback control of midbrain dopamine neurons

Wei Xing Shi, Paula L. Smith, Chen Lun Pun, Barbara Millet, Benjamin S. Bunney

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Dopamine (DA) D1-like receptors are present in pathways implicated in feedback control of midbrain DA neurons. However, stimulation of these receptors either produces no effect on DA cells, or the effect is inconsistent. It is possible that the expression of a D1 feedback effect requires co-activation of D2-like receptors. To test this hypothesis, we recorded extracellularly the spontaneous activity of nigral DA cells in a low cerveau isole rat preparation. SKF38393 and dyhydrexidine, two D1 agonists, were administered systemically to animals pretreated with different doses of the D2 agonist quinpirole. Supporting the hypothesis, the two D1 agonists consistently inhibited DA cells in animals given high doses of quinpirole (≤40 μg/kg, i.v.). However, no significant D1 effect was observed in animals pretreated with only low doses (≤20 μg/kg) of quinpirole. Because low doses of D2 agonists preferentially act on DA autoreceptors, and because the D1 inhibition persisted in animals whose DA autoreceptors were blocked by intranigral application of raclopride, our results suggest that the expression of D1 feedback inhibition requires co-activation of D2-like receptors on DA target neurons, instead of DA neurons themselves. These results, together with the finding that chloral hydrate completely blocked the D1 inhibition, may explain why previous studies have failed to show a consistent D1 effect on DA cells and suggest that drugs designed to act specifically on one subtype of DA receptor may, via feedback pathways, influence the action of endogenous DA on other DA receptor subtypes as well.

Original languageEnglish (US)
Pages (from-to)7988-7994
Number of pages7
JournalJournal of Neuroscience
Volume17
Issue number20
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Dopaminergic Neurons
Mesencephalon
Dopamine
Quinpirole
Autoreceptors
Dopamine Receptors
Raclopride
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Chloral Hydrate
Dopamine D1 Receptors
Substantia Nigra
Pharmaceutical Preparations

Keywords

  • D1
  • D2
  • DA neuron
  • Dyhydrexidine
  • Feedback pathway
  • Single-unit recording
  • SKF38393
  • Striatonigral
  • Substantia nigra
  • Synergistic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Shi, W. X., Smith, P. L., Pun, C. L., Millet, B., & Bunney, B. S. (1997). D1-D2 interaction in feedback control of midbrain dopamine neurons. Journal of Neuroscience, 17(20), 7988-7994.

D1-D2 interaction in feedback control of midbrain dopamine neurons. / Shi, Wei Xing; Smith, Paula L.; Pun, Chen Lun; Millet, Barbara; Bunney, Benjamin S.

In: Journal of Neuroscience, Vol. 17, No. 20, 01.01.1997, p. 7988-7994.

Research output: Contribution to journalArticle

Shi, WX, Smith, PL, Pun, CL, Millet, B & Bunney, BS 1997, 'D1-D2 interaction in feedback control of midbrain dopamine neurons', Journal of Neuroscience, vol. 17, no. 20, pp. 7988-7994.
Shi WX, Smith PL, Pun CL, Millet B, Bunney BS. D1-D2 interaction in feedback control of midbrain dopamine neurons. Journal of Neuroscience. 1997 Jan 1;17(20):7988-7994.
Shi, Wei Xing ; Smith, Paula L. ; Pun, Chen Lun ; Millet, Barbara ; Bunney, Benjamin S. / D1-D2 interaction in feedback control of midbrain dopamine neurons. In: Journal of Neuroscience. 1997 ; Vol. 17, No. 20. pp. 7988-7994.
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