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

Fingerprint

Corpus Striatum
Autoreceptors
Acetylcholine
Dopamine
Nicotinic Receptors
Cholinergic Receptors
Perfusion
Raclopride
Quinpirole
Ligand-Gated Ion Channels
Microdialysis
Nucleus Accumbens
G-Protein-Coupled Receptors
Nicotine
Immunoprecipitation
Membranes

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Quarta, D., Ciruela, F., Patkar, K., Borycz, J., Solinas, M., Lluis, C., ... 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

Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release. / Quarta, Davide; Ciruela, Francisco; Patkar, Kshitij; Borycz, Janusz; Solinas, Marcello; Lluis, Carme; Franco, Rafael; Wise, Roy A.; Goldberg, Steven R.; Hope, Bruce T.; Woods, Amina S.; Ferré, Sergi.

In: Neuropsychopharmacology, Vol. 32, No. 1, 01.01.2007, p. 35-42.

Research output: Contribution to journalArticle

Quarta, D, Ciruela, F, Patkar, K, Borycz, J, Solinas, M, Lluis, C, Franco, R, Wise, RA, Goldberg, SR, Hope, BT, Woods, AS & Ferré, S 2007, 'Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release', Neuropsychopharmacology, vol. 32, no. 1, pp. 35-42. https://doi.org/10.1038/sj.npp.1301103
Quarta, Davide ; Ciruela, Francisco ; Patkar, Kshitij ; Borycz, Janusz ; Solinas, Marcello ; Lluis, Carme ; Franco, Rafael ; Wise, Roy A. ; Goldberg, Steven R. ; Hope, Bruce T. ; Woods, Amina S. ; Ferré, Sergi. / Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release. In: Neuropsychopharmacology. 2007 ; Vol. 32, No. 1. pp. 35-42.
@article{9d9c4448b1c54749a3da5ba7187a48a9,
title = "Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release",
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.",
keywords = "Autoreceptor, Dopamine D receptor, Dopamine release, Heteroreceptor, Nicotinic acetylcholine receptor, Striatum",
author = "Davide Quarta and Francisco Ciruela and Kshitij Patkar and Janusz Borycz and Marcello Solinas and Carme Lluis and Rafael Franco and Wise, {Roy A.} and Goldberg, {Steven R.} and Hope, {Bruce T.} and Woods, {Amina S.} and Sergi Ferr{\'e}",
year = "2007",
month = "1",
day = "1",
doi = "10.1038/sj.npp.1301103",
language = "English (US)",
volume = "32",
pages = "35--42",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Heteromeric nicotinic acetylcholine-dopamine autoreceptor complexes modulate striatal dopamine release

AU - Quarta, Davide

AU - Ciruela, Francisco

AU - Patkar, Kshitij

AU - Borycz, Janusz

AU - Solinas, Marcello

AU - Lluis, Carme

AU - Franco, Rafael

AU - Wise, Roy A.

AU - Goldberg, Steven R.

AU - Hope, Bruce T.

AU - Woods, Amina S.

AU - Ferré, Sergi

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

KW - Autoreceptor

KW - Dopamine D receptor

KW - Dopamine release

KW - Heteroreceptor

KW - Nicotinic acetylcholine receptor

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=33845690518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845690518&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1301103

DO - 10.1038/sj.npp.1301103

M3 - Article

C2 - 16710311

AN - SCOPUS:33845690518

VL - 32

SP - 35

EP - 42

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 1

ER -