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The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors

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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.

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Acknowledgments

We very much appreciate Arantxa Martínez Férriz for her technical assistance. This study was supported by the Fondo de Investigación Sanitaria (FIS), Instituto Salud Carlos III, and Grant No. 011/00737. The CIBERSAM is an initiative of the Instituto de Salud Carlos III. Guillermo Ponce has received research support from Otsuka Pharmaceutical Co, LTD. FIS, and Otsuka Pharmaceutical had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario, Avda. Andalucía s/n, 28041, Madrid, Spain

    Guillermo Ponce, Adolfo Quiñones-Lombraña, Noelia Guerra Martín-Palanco, Miguel Ángel Jiménez-Arriero, Tomás Palomo & Janet Hoenicka

  2. Red de Trastornos Adictivos (RTA), Madrid, Spain

    Guillermo Ponce

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Adolfo Quiñones-Lombraña, Noelia Guerra Martín-Palanco, Miguel Ángel Jiménez-Arriero, Tomás Palomo & Janet Hoenicka

  4. Program of Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe, C/Eduardo Primo Yúfera 3, 46012, Valencia, Spain

    Estrella Rubio-Solsona & Janet Hoenicka

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  1. Guillermo Ponce
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  2. Adolfo Quiñones-Lombraña
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  3. Noelia Guerra Martín-Palanco
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  4. Estrella Rubio-Solsona
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  5. Miguel Ángel Jiménez-Arriero
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  6. Tomás Palomo
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  7. Janet Hoenicka
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Correspondence to Janet Hoenicka.

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Ponce, G., Quiñones-Lombraña, A., Martín-Palanco, N.G. et al. The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors. Neurotox Res 29, 345–350 (2016). https://doi.org/10.1007/s12640-015-9545-9

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  • DOI: https://doi.org/10.1007/s12640-015-9545-9

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