| Autor: |
Szopa A; Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland., Herbet M; Chair and Department of Toxicology, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland., Poleszak E; Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland., Bogatko K; Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland., Ostrowska-Leśko M; Chair and Department of Toxicology, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland., Świąder K; Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland., Szponar J; Clinical Department of Toxicology and Cardiology, Stefan Wyszyński Regional Specialist Hospital in Lublin, Al. Kraśnicka 100, 20-550 Lublin, Poland.; Toxicology Clinic, Medical University of Lublin, Al. Kraśnicka 100, 20-550 Lublin, Poland., Serefko A; Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland. |
| Abstrakt: |
The main goal of this study was to determine the antidepressant-like potential of the co-administration of sodium selenite (Se) and the selective adenosine A1 and A2A antagonists DPCPX and istradefylline (IST), respectively, in mice despair tests. Biochemical studies were performed to elucidate the action mechanisms of the investigated treatment strategies. The results confirmed that, when administered by itself, Se exerts an antidepressant-like effect in the FST and TST and that this activity is dose-dependent. Further experiments demonstrated that Se (0.25 mg/kg) significantly enhanced the activity of mice in both tests when co-administered with DPCPX (1 mg/kg) and IST (0.5 mg/kg) at doses which would be ineffective if administered individually. Our research revealed that neither DPCPX, IST, nor Se or combinations of the tested substances induced significant changes in the brain-derived neurotrophic factor (BDNF) levels in mice serum vs. the NaCl-treated group. However, we observed a decrease in the mRNA level of antioxidant defense enzymes. Molecular studies also showed changes in the expression of the Slc6a15 , Comt , and Adora1 genes, particularly after exposure to the combination of Se and DPCPX, which indicates a beneficial effect and may help to explain the key mechanism of the antidepressant effect. The combination of Se with substances attenuating adenosine neurotransmission may become a new therapeutic strategy for patients with depression. |
