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

• Published in: International journal of molecular sciences Vol. 22; no. 4; p. 1840
• Main Authors: Szopa, Aleksandra, Bogatko, Karolina, Herbet, Mariola, Serefko, Anna, Ostrowska, Marta, Wośko, Sylwia, Świąder, Katarzyna, Szewczyk, Bernadeta, Wlaź, Aleksandra, Skałecki, Piotr, Wróbel, Andrzej, Mandziuk, Sławomir, Pochodyła, Aleksandra, Kudela, Anna, Dudka, Jarosław, Radziwoń-Zaleska, Maria, Wlaź, Piotr, Poleszak, Ewa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 12-02-2021; MDPI AG
• Subjects: Adenosine A1 Receptor Antagonists - pharmacology; Adenosine A2 Receptor Antagonists - pharmacology; Animals; antidepressant activity; Behavior, Animal - drug effects; DPCPX; istradefylline; magnesium; Magnesium - pharmacology; Male; Mice; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A2A - metabolism; Xanthines - pharmacology; zinc; Zinc - pharmacology; istradefylline; magnesium; DPCPX; zinc; antidepressant activity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22041840

The purpose of the study was to investigate whether the co-administration of Mg
and Zn
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 Mg
and Zn
manifested in an antidepressant-like effect. The reduction of the BDNF serum level after co-administration of DPCPX and istradefylline with Mg
and Zn
was noted. Additionally, Mg
or Zn
, both alone and in combination with DPCPX or istradefylline, causes changes in
expression, DPCPX or istradefylline co-administered with Zn
increases
expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on
expression. Moreover, the changes obtained in
,
,
expression show that DPCPX-Mg
, DPCPX-Zn
, istradefylline-Mg
and istradefylline-Zn
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.