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

Abstract

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 Adora1 expression, DPCPX or istradefylline co-administered with Zn2+ increases Slc6a15 expression as compared to a single-drug treatment, co-administration of tested agents does not have a more favourable effect on Comt expression. Moreover, the changes obtained in Ogg1, MsrA, Nrf2 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.

Effects of Selen on the Antidepressant-like Activity of Agents Affecting the Adenosinergic Neurotransmission

“…None of the tested substances or their co-administration significantly changed rodents' performances when they were put into cages of the monitoring device. This was in line with our previous studies on DPCPX [41,43] and IST [41].…”

“…The doses and administration schedule for the tested substances were selected based on the literature data and our previous research [29,[40][41][42][43]. The FST was carried out according to the procedure described in detail previously [40,41,97].…”

“…The doses and administration schedule for the tested substances were selected based on the literature data and our previous research [29,[40][41][42][43]. The FST was carried out according to the procedure described in detail previously [40,41,97]. The test was video recorded, and the total duration of immobility was measured between the 2nd and the 6th min of the test by two blind observers.…”

Antidepressant-like Effects of Combined Fluoxetine and Zinc Treatment in Mice Exposed to Chronic Restraint Stress Are Related to Modulation of Histone Deacetylase

“…Locomotor activity was measured using an Opto-Varimex-4 Auto-Track (Columbus Instruments, Ohio, USA). The movements of the mice were analyzed in transparent cages (3) covered with lids, a set of four infrared emitters with 16 laser beams each, and four detector tracking and monitoring [ 90 ]. Movement detection was analyzed for each mouse separately for 6 min, which is correlated with the TST test.…”

Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

“…Zinc (Zn) is considered to one of the most significant microelements that affects the nervous system. So far, many analyses and studies investigating the relationship between Zn and depression have been carried out [ 114 , 115 , 116 ]. Undoubtedly, as confirmed by some researchers, regular and appropriate dosage of Zn reduces the symptoms and disorders caused by depression [ 117 ].…”