Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release

Davide Quarta, Francisco Ciruela, Kshitij Patkar, Janusz Borycz, Marcello Solinas, Carme Lluis, Rafael Franco, Roy A. Wise, Steven R. Goldberg, Bruce T. Hope, Amina S. Woods, Sergi Ferré

Research output: Contribution to journalArticle

Abstract

In the striatum, dopamine and acetylcholine (ACh) modulate dopamine release by acting, respectively, on dopamine D2 autoreceptors and nicotinic ACh (nACh) heteroreceptors localized on dopaminergic nerve terminals. The possibility that functional interactions exist between striatal D2 autoreceptors and nACh receptors was studied with in vivo microdialysis in freely moving rats. Local perfusion of nicotine in the ventral striatum (shell of the nucleus accumbens) produced a marked increase in the extracellular levels of dopamine, which was completely counteracted by co-perfusion with either the non-α7 nACh receptor antagonist dihydro-β-erythroidine or the D2-3 receptor agonist quinpirole. Local perfusion of the D 2-3 receptor antagonist raclopride produced an increase in the extracellular levels of dopamine, which was partially, but significantly, counteracted by coperfusion with dihydro-β-erythroidine. These findings demonstrate a potent crosstalk between G protein-coupled receptors and ligand-gated ion channels in dopaminergic nerve terminals, with the D 2 autoreceptor modulating the efficacy of non-α7 nACh receptor-mediated modulation of dopamine release. We further demonstrate physical interactions between β2 subunits of non-α7 nicotinic acetylcholine receptors and D2 autoreceptors in co-immunoprecipitation experiments with membrane preparations from co-transfected mammalian cells and rat striatum. These results reveal that striatal non-α7 nicotinic acetylcholine receptors form part of heteromeric dopamine autoreceptor complexes that modulate dopamine release.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalNeuropsychopharmacology
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • Autoreceptor
  • Dopamine D receptor
  • Dopamine release
  • Heteroreceptor
  • Nicotinic acetylcholine receptor
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Quarta, D., Ciruela, F., Patkar, K., Borycz, J., Solinas, M., Lluis, C., Franco, R., Wise, R. A., Goldberg, S. R., Hope, B. T., Woods, A. S., & Ferré, S. (2007). Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release. Neuropsychopharmacology, 32(1), 35-42. https://doi.org/10.1038/sj.npp.1301103