Inibição de ciclooxigenase-2 (COX-2) em camundongos infantis saudáveis: consequências sobre o comportamento e o perfil oxidativo

Abstract

In the central nervous system, cyclooxygenase 2 (COX-2) is a constitutive enzyme, expressed by neurons from different brain regions, which acts in the maintenance of neural homeostasis, modulating synaptic plasticity and the generation of new neurons. Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs of choice that act to inhibit COX enzymes, with nimesulide (NMS) being a drug of this class. Several studies have demonstrated the role of these enzymes in neurological and neuropsychiatric disorders such as Parkinson's Disease, Alzheimer's Disease, epilepsy, depression and

schizophrenia. Thus, the aim of the present work was to investigate the effects of COX- 2 inhibition in healthy infant mice on behavioral and biochemical criteria, using NMS as

a pharmacological blockade tool. For this, male Swiss infant mice, aged between 21 and 34 days, were used. The animals were randomly divided into four groups: (1) Vehicle, (2) NMS 2.5mg/kg, (3) NMS 5mg/kg and (4) NMS 10mg/kg. Two injections of NMS/Vehicle were administered intraperitoneally daily. Throughout the experiment, the body mass of the animals was recorded daily and they were subjected to behavioral tests: open field test (OFT), elevated plus maze (EPM), light/dark box test (LDBT) and novel object recognition test (NORT). In addition, brain samples were collected for biochemical analyses. The results demonstrated the induction of oxidative stress with increased levels of lipid peroxidation in the cortex and hippocampus, as well as the expression of an anxiogenic behavior, observed in the EPM, possibly potentiated by fear. In the NORT, the animals of the NMS 5mg/kg group showed a deficit in the memory of recognizing new objects, and consequently, in the short-term memory. Thus, our results demonstrated that the in vivo inhibition of COX-2 in infant animals induces an anxious-like behavior possibly potentiated by fear, but does not affect the exploration and locomotion of these animals. Furthermore, COX-2 inhibition induced cortical and hippocampal oxidative stress. Therefore, the inhibition of COX-2 in infantile and non-inflamed animals may compromise cognitive functions such as memory and learning, as well as alter the cerebral oxidative profile.