The Interaction of Selective A1 and A2A adenosine Receptor Antagonists with Magnesium and Zinc Ions in Mice: Behavioural, Biochemical and Molecular Studies

• Main Authors: Aleksandra Szopa, Karolina Bogatko, Mariola Herbet, Anna Serefko, Marta Ostrowska, Sylwia Wośko, Katarzyna Świąder, Bernadeta Szewczyk, Aleksandra Wlaź, Piotr Skałecki, Andrzej Wróbel, Sławomir Mandziuk, Aleksandra Pochodyła, Anna Kudela, Jarosław Dudka, Maria Radziwoń-Zaleska, Piotr Wlaź, Ewa Poleszak
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: DPCPX; istradefylline; magnesium; zinc; antidepressant activity
• Online Access: https://www.mdpi.com/1422-0067/22/4/1840
• ISSN: 1661-6596; 1422-0067

The purpose of the study was to investigate whether the co-administration of Mg²⁺ and Zn²⁺ with selective A1 and A2A receptor antagonists might be an interesting antidepressant strategy. Forced swim, tail suspension, and spontaneous locomotor motility tests in mice were performed. Further, biochemical and molecular studies were conducted. The obtained results indicate the interaction of DPCPX and istradefylline with Mg²⁺ and Zn²⁺ manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg²⁺ and Zn²⁺ was noted. Additionally, Mg²⁺ or Zn²⁺, both alone and in combination with DPCPX or istradefylline, causes changes in <i>Adora1 </i>expression, DPCPX or istradefylline co-administered with Zn²⁺ increases <i>Slc6a15</i> expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on <i>Comt </i>expression. Moreover, the changes obtained in <i>Ogg1, MsrA, Nrf2 </i>expression show that DPCPX-Mg²⁺, DPCPX-Zn²⁺, istradefylline-Mg²⁺ and istradefylline-Zn²⁺co-treatment may have greater antioxidant capacity benefits than administration of DPCPX and istradefylline alone. It seems plausible that a combination of selective A1 as well as an A2A receptor antagonist and magnesium or zinc may be a new antidepressant therapeutic strategy.