The Positive Synergism of CPT and MK-801 in Behavioral Tests and in Reduction of Environmental Stress and Redox Signaling Changes in Mice Cerebral Cortex

Background: Depressive disorders are associated with oxidative stress. Therefore, it is interesting if antidepressants can affect redox equilibrium and signaling. The first step of our study was to determine the influence of the adenosine system on the antidepressant-like activity of noncompetitive antagonist of the NMDA (N-methyl-d-aspartate) receptor complex - dizocilpine (MK- 801). To this aim, two behavioral tests commonly used to assess the antidepressant capability of drugs - the forced swim test (FST) and tail suspension test (TST), were performed. Locomotor activity was estimated to verify and exclude false positive/negative results in the FST and TST. To examine whether antidepressants affect redox equilibrium, we have investigated lipid peroxidation products (LPO), GSH (glutathione), GSSG (glutathione disulfide), NADP+ (nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate) in the cerebral cortex of mice following administration of CPT (8-cyclopentyl-1,3-dimethylxanthine) and MK-801 (dizocilpine) under environmental stress conditions.

Method: The experiments were carried out using male Albino Swiss mice (25-30 g). The drugs were administered ip., alone and simultaneously, 60 min before tests.

Results: The behavioural tests results showed that CPT (3 mg/kg) potentiated the antidepressant-like activity of MK-801 (0.05 mg/kg) and the observed effects were not due to the increase in mice locomotor activity. Positive synergism of CPT and MK-801 in reduction of environmental stress conditions was revealed. In this group an increase in GSH and GSSG without changes in GSH/GSSG ratio and reduction of LPO was found. The level of lipid peroxidation products was also decreased in group receiving CPT and MK-801 separately.

Conclusion: Examined antidepressant agents may increase antioxidant defences however further studies are needed with different range of time.