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 D(2) autoreceptors and nicotinic ACh (nACh) heteroreceptors localized on dopaminergic nerve terminals. The possibility that functional interactions exist between striatal D(2) 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-alpha(7) nACh receptor antagonist dihydro-beta-erythroidine or the D(2-3) 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-beta-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-alpha(7) nACh receptor-mediated modulation of dopamine release. We further demonstrate physical interactions between beta(2) subunits of non-alpha(7) nicotinic acetylcholine receptors and D(2) autoreceptors in co-immunoprecipitation experiments with membrane preparations from co-transfected mammalian cells and rat striatum. These results reveal that striatal non-alpha(7) nicotinic acetylcholine receptors form part of heteromeric dopamine autoreceptor complexes that modulate dopamine release.
authors.affiliation: Behavioral Neuroscience Branch, National Institute on Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Quarta
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Kshitij
authors.initials: K
authors.lastname: Patkar
authors.forename: Janusz
authors.initials: J
authors.lastname: Borycz
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.forename: Carme
authors.initials: C
authors.lastname: Lluis
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Roy A
authors.initials: RA
authors.lastname: Wise
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
authors.forename: Amina S
authors.initials: AS
authors.lastname: Woods
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D017448:Receptors, Dopamine D2; D011978:Receptors, Nicotinic; D019257:Quinpirole; D004079:Dihydro-beta-Erythroidine; D020891:Raclopride; D009538:Nicotine; D004298:Dopamine