title: The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors.
abstract: The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether Ankk1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in murine brain after dopaminergic treatments. We found that Ankk1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon Ankk1 mRNA (1.004 ± 0.580-fold; t: 0.015, df: 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant Ankk1 mRNA downregulation (0.606 ± 0.057-fold; t: 2.786, df: 10, P = 0.02 and 0.588 ± 0.130-fold; t: 2.394, df: 11, P = 0.036, respectively). With respect the Ankk1 proteins profile, no effects were found after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of Ankk1 by specific pathways.
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain.|Red de Trastornos Adictivos (RTA), Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ponce
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Quiñones-Lombraña
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Noelia Guerra
authors.initials: NG
authors.lastname: Martín-Palanco
authors.affiliation: Program of Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Rubio-Solsona
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Jiménez-Arriero
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Palomo
authors.affiliation: Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain. jhoenicka@gmail.com.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. jhoenicka@gmail.com.|Program of Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain. jhoenicka@gmail.com.
authors.forename: Janet
authors.initials: J
authors.lastname: Hoenicka
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage; D000818:Animals; D001058:Apomorphine; D000068180:Aripiprazole; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011804:Quinolines; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D013764:Tetrahydronaphthalenes; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C000600618:DRD2 protein, mouse; C583261:Drd1 protein, mouse; D011804:Quinolines; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000068180:Aripiprazole; D017346:Protein Serine-Threonine Kinases; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane
keywords: Addiction; Ankk1/Drd2; Drd1; Drd3; TaqIA