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.
2017
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 non-competitive antagonist of the NMDA 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, GSH, GSSG, NADPH and NADP+ in
the cerebral cortex of mice following administration of CPT and MK-801 under
environmental stress conditions.
Methods: 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.
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