title: Acute drug-induced spine changes in the nucleus accumbens are dependent on β-adducin.
abstract: Chronic modifications of dopamine transmission alter striatal dendritic spines. Here, we show that spine density and length are increased in the nucleus accumbens 24 h after a single injection of caffeine or quinpirole, a dopamine D2/D3 dopamine receptors agonist, whereas the dopamine antagonist haloperidol has opposite effects. These effects are absent in mice lacking β-adducin, a protein that stabilizes actin/spectrin cortical cytoskeleton and modulates synaptic plasticity. Phosphorylation of adducin (Ser713 in β-adducin), which disrupts actin/spectrin interaction, is increased by quinpirole, haloperidol, or caffeine. We previously demonstrated that DARPP-32 interacts with β-adducin and facilitates its phosphorylation. Quinpirole increased DARPP-32 phosphorylation at Thr75 and haloperidol at Ser97, two modifications that can have similar consequences on adducin phosphorylation through distinct mechanisms. Experiments in DARPP-32 mutant mice confirmed that the apparently paradoxical similar effects of quinpirole and haloperidol on adducin phosphorylation may result from differential effects of these drugs on DARPP-32 phosphorylation at Thr75 and Ser97. Our data provide novel insights on how a single dose of widely used psychoactive drugs can affect spine plasticity in the nucleus accumbens, a component of the reward system.
authors.affiliation: Inserm UMR-S 839, Paris, 75005, France; Sorbonne Universités, UPMC, Université Paris 06, Paris, 75005, France; Institut du Fer à Moulin, Paris, 75005, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Engmann
authors.affiliation: Inserm UMR-S 839, Paris, 75005, France; Sorbonne Universités, UPMC, Université Paris 06, Paris, 75005, France; Institut du Fer à Moulin, Paris, 75005, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.affiliation: Inserm UMR-S 839, Paris, 75005, France; Sorbonne Universités, UPMC, Université Paris 06, Paris, 75005, France; Institut du Fer à Moulin, Paris, 75005, France. Electronic address: jean-antoine.girault@inserm.fr.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003598:Cytoskeletal Proteins; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D000099291:Adducins
chemical_list: D002110:Caffeine; D003598:Cytoskeletal Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D006220:Haloperidol; D008840:Microfilament Proteins; D011619:Psychotropic Drugs; D019257:Quinpirole; C559159:Add2 protein, mouse; D000099291:Adducins; C497929:Ppp1r1b protein, mouse
keywords: Antipsychotics; Caffeine; DARPP-32; Dendritic spines; Dopamine; Dopamine D2 receptors; Phosphorylation; Striatum